Stefan Sarafianos, PhD

Chancellor's Chair of Excellence in Molecular Virology, Professor


Molecular Microbiology & Immunology


E-mail


(573) 882-4338


Google Scholar Homepage

Fields of Interest

  • Viral replication and entry
  • Antivirals

Education

  • Ph.D. 1993, Georgetown University

Research Statement

Our laboratory unravels mechanisms of virus biology, drug action and drug resistance. These basic science studies are fundamentally important as prerequisites for the development of novel treatments of serious diseases.

Significance

Despite breakthroughs in the treatment of viral diseases, they remain enormous public health challenges. Over 30 million people are currently infected with Human Immunodeficiency Virus (HIV). Remarkably, despite the availability of a vaccine for Hepatitis B Virus (HBV), ~400 million individuals are chronically infected and in need of treatment with antivirals. In this era of globalization, worldwide outbreaks of new, emerging, and re-emerging diseases including Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), or Foot-and-Mouth-Disease (FMD) are global threats that have the potential to become an immense burden on the US and world economies.

The introduction of combinations of anti-HIV drugs has significantly decreased HIV-related mortality. Yet, up to 25% of patients receiving first-line therapies in Africa experience virologic failure within the first year of therapy through drug resistance mutations. In the case of HBV there is only a single class of drugs available, and there are currently no approved antiviral treatments for MERS and SARS-Coronavirus, or FMDV infections.

Academic research is the workhorse of drug discovery, as it focuses on fundamental virus biology and molecular interactions that involve viral targets, potential therapeutics, drug resistant proteins, and host factors. In depth understanding of these interactions is needed for innovative and novel drug discoveries and this is an area where we have made significant contributions. Toward that end we use a combination of crystallographic, biochemical, virological approaches to chart the details of molecular recognition during steps of the life cycle of viruses, allowing us to identify and target weak spots.

Stopping the virus in its tracks: Targeting the translocation function of HIV Reverse transcriptase (RT) with EFdA, the most potent anti-HIV drug

Our lab has discovered an ultrapotent mechanism of HIV inhibition. This mechanism is followed by EFdA, a compound that is by far the most potent inhibitor of HIV replication inhibiting HIV at low picomolar concentrations by an innovative mechanism of action and a very promising resistance profile (Kawamoto et al. 2008, Michailidis et al. 2009). EFdA was originally synthesized by Ohrui and recently licensed by Yamasa to Merck for the treatment of HIV infection.

research_sarafianos2Hypersusceptibility of tenofovir- and nonnucleoside RT inhibitor-resistant viruses to EFdA: Since most HIV patients are currently on primarily tenofovir-based therapies, we assessed the effect of EFdA and its analogs on HIVs that are resistant to nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). EFdA suppressed NRTI-resistant viruses with remarkable efficiency and was remarkably effective against the tenofovir-resistant variants. This is highly important because tenofovir is the first line of defense in HIV therapies and a backup drug that works well with tenofovir-resistant viruses would be very valuable. Our recently published relevant manuscript (Michailidis et al. 2013) is among the highest articles ever scored in Retrovirology (a journal ranked #1 in Virology and #16 of 452 in the broader field) and in the top 5% of all of the 2,128,264 articles tracked by Altmetric across all journals. In another recent manuscript (Hachiya et al. 2013) we showed that EFdA acts synergistically with the second generation NNRTI rilpivirine and does not compete with tenofovir. Collectively, these data predict that EFdA would form a formidable combination with tenofovir, and/or rilpivirine and would perform extremely well even with patients that have failed current therapies.

Extraordinary in vivo activity of EFdA: Importantly, our collaborative non-human primate study with Drs. M. Murphey-Corb, Michael Parniak at the University of Pittsburgh and Hiroaki Mitsuya (NIH, University of Kumamoto) established that EFdA has extraordinary activity in vivo. Moreover, no detectable clinical or pathological signs of drug toxicity were observed within 6 months of continuous therapy. Following our exciting data on EFdA, Merck licensed EFdA for preclinical development. Overall, our EFdA-related work (so far 14 relevant publications) has been instrumental for the advancement of EFdA and it has been carried out in collaboration with Drs. Hiroaki Mitsuya (NIH, Kumamoto University), Michael Parniak (University of Pittsburgh), Eiichi Kodama (Tohoku University), and recently Lesa Rohan (University of Pittsburgh). It has been funded by NIH (R01AI076119, R21/R33AI079801, R01AI076119-S1, R01AI076119-S2, R01AI076119-06A1) and amfAR grants.

 

Targeting HIV RNase H, the ‘final frontier’

It is imperative to also identify new drug candidates directed at HIV targets not addressed by current therapeutics, as these are likely to be effective against current drug-resistant HIV strains. HIV RNase H is one such target. None of the clinically approved HIV drugs targets RNH, and there are no RNH inhibitors (RNHIs) in preclinical development. We are spearheading a collaborative effort to discover RNHIs funded by a multi-PI NIH grant (R01 AI100890) for scientists from the University of Missouri, University of Pittsburgh (Dr. Michael Parniak), and University of Minnesota (Dr. Z. Wang), with expertise in structural and computational biology, medicinal chemistry, biochemistry, and virology. Extensive progress has provided the molecular details of different mechanisms of RNH inhibition and is guiding efforts to design and prepare modified compounds, potentially giving rise to new inhibitors with enhanced potency.

 

Novel antivirals for treatment of HBV infection

Our successes with RNHIs against HIV leveraged the discovery of novel antivirals against HBV, which target the RNH activity of HBV. Despite the availability of an HBV vaccine, ~400 million people are chronically infected by HBV and are treated with drugs from a single family, NRTIs. There is also interferon, which does not target the virus itself and is not as effective. Unlike in HIV treatments, there is no other class of drugs that targets the virus itself. Hence, discovery of compounds that inhibit the HBV RNH would present a breakthrough in HBV treatment and allow meaningful combination therapies equivalent to Highly Active Antiretrovial Therapies in HIV that dramatically decreased HIV-related deaths. In collaboration with J. Tavis we recently identified the first compound that targets RNH and blocks HBV replication in cell-based assays (PLoS Pathogens 9(1):e1003125). However, to further build on these efforts, reagents are needed for extensive testing of compounds. Hence, based on homology modeling using our previously solved RNH structures from HIV and XMRV, we have now designed and constructed several HBV RNH constructs (invention disclosure in preparation). In exciting data (to be published), we have prepared a soluble and enzymatically active HBV RNH that can be used for drug discovery. Using this novel reagent we have tested ~100 of our potential RNHIs and identified compounds with anti-HBV properties. Ongoing and future studies in collaboration with Drs. Z. Wang (U Minnesota) and Michael Parniak (U Pittsburgh) focus on improvement of the early leads towards the development of novel-HBV inhibitors of exceptional potency that will change HBV treatments and provide additional options to patients. We are also collaborating on HBV drug discovery with Dr. Hiroaki Mitsuya (NIH, Kumamoto University).

 

Role of HIV capsid (CA) in HIV biology- Targeting CA for novel antiviral strategies

research_sarafianos3CA is a structural protein essential for early and late events of HIV replication. Its multiple roles in infection and pathogenesis are not entirely understood. CA is an attractive therapeutic target since proper capsid formation is required for virus infectivity. We have discovered 18E8 (unpublished, to be patented), a compound with antiviral properties that interferes with the rate of CA multimerization. We have shown 18E8 to work by a novel mechanism and recently received an NIH grant to study this mechanism. Importantly, during this study we have solved the crystal structure of native hexameric full length HIV CA, an elusive structure for ~20 years. The structure provides insights into HIV biology and has resulted into collaborations with distinguished scientists in the field. Future efforts focus on providing the molecular details of CA interactions with cellular host proteins and improving our early inhibitors towards the development of innovative CA-targeting HIV therapeutics.

 

Discovery and characterization of a new mechanism of HIV multi-drug resistance

In collaboration with Japanese clinical scientists and independently from competing groups we helped demonstrate that RT mutation N348I causes resistance to drugs that belong to multiple classes of antiretrovirals (PI: Eiichi Kodama) (Hachiya et al. 2008). Our findings contributed to the redesign of clinical tools that detect HIV resistance mutations in patients and define the course of therapies. We also discovered new RT mutati on K70Q that causes multidrug resistance to tenofovir-based regimens (Hachiya et al, 2011). Ongoing and future efforts focus on the study of polymorphisms in various HIV clades towards elucidating drug resistance differences among various HIV subtypes, obtaining knowledge that should help optimize treatment strategies.

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Novel methods for identification of drug resistance in HIV and HBV patients

In a related effort on drug resistance, we accepted an invitation for collaboration by Genematrix, a publicly traded Korean company, which manufactures mass spectrometry instrumentation. Based on our experience with drug resistance in HIV and other viruses Genematrix and ourgroup published a method that increases the sensitivity of current drug-resistance detection protocols, so that we can detect earlier drug resistance mutations and accordingly direct changes in therapeutic regimens (funding by 5-yr grant from the Korean government/Genematrix).

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Engineering anti-HIV antibodies

We have solved the crystal structure of anti-HIV antibody KD-247 that is currently in Phase II clinical trials. To our knowledge, this structure is of the highest resolution reported for any humanized antibody. Our data will help design improved antibodies that work better against more types of HIV (broader neutralization). Also, using phage display we discovered broadly neutralizing antibody fragments (funding by NIH grant R21 AI094715).

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Discovery and characterization of novel anti-SARS and anti-MERS inhibitors

We have discovered, characterized, and patented a helicase inhibitor that has antiviral properties specifically against several coronaviruses (SARS-CoV, MERS-CoV, MHV) (potential pan-coronaviral inhibitor-Adedeji et al, 2014) but not against other RNA viruses (Adedeji etal., 2012a,b,c). We have also identified 3 SARS-Entry inhibitors that act by 3 distinct mechanisms of action (Adedeji et al, J. Virol 2013). These data have received extensive attention and have been published in 8 manuscripts and so far 1 patent and 1 invention disclosure.

 

Discovery of FMDV inhibitors

FMDV is a picornavirus that infects cloven-hoofed animals and leads to severe losses in livestock. We discovered and characterized a novel inhibitor of FMDV replication. Through collaboration with USDA scientists at Plum Island NY (Dr. E. Rieder and colleagues) we demonstrated antiviral activity of the compound (Durk et al, 2010), and now have an international patent for its use. We have shown that the novel targeted pocket is conserved in other viruses which we are currently studying.

 

Discovery of multiple assays for optimal combinations of HCV inhibitors

We have recently started a project on HCV in collaboration with world-leader in the field Dr. Charles Rice (Rockefeller University) and obtained 5-yr NIH funding R01AI099284. We have established novel microscopy-based assays for identifying optimal combinations of anti-HCV drugs. We are using these novel technologies to address the effect of host factors in the HCV life cycle. These studies were initiated by research faculty in our lab Dr. R. Ralston, who is now a Research Professor at Kansas Univ. Medical Center.

 

Advancing MissouriFeatured Video on “Combating Foot and Mouth Disease”

Publications

Stefan Sarafianos is the author of 121 manuscripts, including 11 invited reviews. 81 of these manuscripts are after joining MU. He is also the author of 22 structures deposited at the PDB. Select publications are listed below – for a PUBMED list of published work follow this link.

Crystal Structures at the Protein Data Base (PDB)

  1. Takamatsu Y, Tanaka Y, Kohgo S, Murakami S, Singh K, Das D, Venzon DJ, Amano M, Kuwata N, Aoki M, Delino NS, Hayashi S, Takahashi S, Sukenaga Y, Haraguchi K, Sarafianos SG, Maeda K, and Mitsuya H. 2015. “4’-Modified nucleoside analogs: Potent inhibitors active against entecavir-resistant hepatitis B virus.” Hepatology 62, 1024-1036. PMCID: PMC4589464.
  2. Gres AT, Kirby KA, KewalRamani VN, Tanner JJ, Pornillos O, and Sarafianos SG. 2015. “X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability.” Science 349, 99-103. PMCID: PMC4584149
  3. Stoddart CA, Galkina SA, Joshi P, Kosikova G, Moreno ME, Rivera JM, Sloan B, Reeve AB, Sarafianos SG, Murphey-Corb M, Parniak MA. 2015. “Oral Administration of the Nucleoside EFdA (4′ -Ethynyl-2-Fluoro-2′ -Deoxyadenosine) Provides Rapid Suppression of HIV Viremia in Humanized Mice and Favorable Pharmacokinetic Properties in Mice and the Rhesus Macaque.” Antimicrob. Agents Chemother 59, 4190-4198. PMCID: PMC4468726.
  4. Ferrer-Orta C, de la Higuera I, Caridi F, Sánchez-Aparicio MT, Moreno E, Perales C, Singh K, Sarafianos SG, Sobrino F, Domingo E, Verdaguer N. 2015. “Multifunctionality of a picornavirus polymerase domain: nuclear localization signal and nucleotide recognition”. J Virol 89, 6848-59. PMCID: PMC4468482.
  5. Liu D, Ji J, Ndongwe TP, Michailidis E, Rice CM, Ralston R, Sarafianos SG. 2015. “Fast HCV RNA elimination and NS5A redistribution by NS5A inhibitors studied by a multiplex assay approach”. Antimicrob Agents Chemother 59, 3482-92. PMCID: PMC4432190.
  6. Zhang W, Hu M, Shi Y, Gong T, Dezzutti CS, Moncla B, Sarafianos SG, Parniak MA, Rohan LC. 2015. “Vaginal Microbicide Film Combinations of Two Reverse Transcriptase Inhibitors, EFdA and CSIC, for the Prevention of HIV-1 Sexual Transmission”. Pharm Res 32, 2960-72. PMCID: PMC4529374.
  7. Strauss KA, Jinks RN, Puffenberger EG, Venkatesh S, Singh K, Cheng I, Mikita N, Thilagavathi J, Lee J, Sarafianos S, Benkert A, Koehler A, Zhu A, Trovillion V, McGlincy M, Morlet T, Deardorff M, Innes AM, Prasad C, Chundley AE, Lee IN, and Suzuki CK. 2015. “CODAS Syndrome is Associated with Mutations of LONP1, Encoding Mitochondrial AAA(+) Lon Protease.” Am. J. Hum. Genet. 96, 121-135. PMCID: PMC4289676.
  8. Singh K, Flores JA, Kirby KA, Neogi U, Sonnerborg A, Hachiya A, Das K, Arnold E, McArthur C, Parniak M, and Sarafianos SG. 2014. “Drug Resistance in Non-B Subtype HIV-1: Impact of HIV-1 Reverse Transcriptase Inhibitors.” Viruses. 6 (9), 3535-3562. PMCID: PMC4189038.
  9. Adedeji AO, Sarafianos SG. 2014.  Antiviral drugs specific for coronaviruses in preclinical development.  Curr Opin Virol. 2014 Jul 2;8C:45-53. doi: 10.1016/j.coviro.2014.06.002. [Epub ahead of print] Review.
  10. Michailidis E, Huber AD, Ryan EM, Ong YT, Leslie MD, Matzek KB, Singh K, Marchand B, Hagedorn AN, Kirby KA, Rohan LC, Kodama EN, Mitsuya H, Parniak MA, and Sarafianos SG.  2014.  4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms.  J Biol Chem. 2014 Jun 26. pii: jbc.M114.562694. [Epub ahead of print]
  11. Huber AD, Michailidis E, Schultz ML, Ong YT, Bloch N, Puray-Chavez MN, Leslie MD, Ji J, Lucas AD, Kirby KA, Landau NR, and Sarafianos SG.  2014. SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.  Antimicrob Agents Chemother. 2014 May 27. pii: AAC.02745-14. [Epub ahead of print]
  12. Adedeji AO, Singh K, Kassim A, Coleman CM, Elliott R, Weiss SR, Frieman MB,  and  Sarafianos SG. 2014.  Evaluation of SSYA10-001 as a Replication Inhibitor of SARS, MHV and MERS Coronaviruses.  Antimicrob Agents Chemother. 2014 May 19. pii: AAC.02994-14. [Epub ahead of print]
  13. Zhang W, Parniak MA, Sarafianos SG, Empey PE, Rohan LC.  2014.  In vitro transport characteristics of EFdA, a novel nucleoside reverse transcriptase inhibitor using Caco-2 and MDCKII cell monolayers.  Eur J Pharmacol.  2014 Jun 5;732:86-95. doi: 10.1016/j.ejphar.2014.03.022. Epub 2014 Mar 29.
  14. Muftuoglu Y, Sohl CD, Mislak AC, Mitsuya H, Sarafianos SG, Anderson KC.  2014. Probing the molecular mechanism of action of the HIV-1 reverse transcriptase inhibitor 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) using pre-steady-state kinetics.  Antiviral Res. Jun;106:1-4. doi: 10.1016/j.antiviral.2014.03.001. Epub 2014 Mar 12.
  15. Zhang W, Parniak MA, Sarafianos SG, Cost MR, Rohan LC.  2014.  Development of a vaginal delivery film containing EFdA, a novel anti-HIV nucleoside reverse transcriptase inhibitor.  Int J Pharm. 2014 Jan 30;461(1-2):203-13. doi: 10.1016/j.ijpharm.2013.11.056. Epub 2013 Dec 9.
  16. Das K, Sarafianos SG, Arnold E.  2013.  Structural requirements for RNA degradation by HIV-1 reverse transcriptase.  Nat Struct Mol Biol. 2013 Dec;20(12):1341-2. doi: 10.1038/nsmb.2725. No abstract available.
  17. Adedeji AO, Sarafianos SG.  2013.  Future treatment strategies for novel Middle East respiratory syndrome coronavirus infection.  Future Med Chem. 2013 Dec;5(18):2119-22. doi: 10.4155/fmc.13.183. No abstract available.
  18. Kirby KA, Michailidis E, Fetterly TL, Steinbach MA, Singh K, Marchand B, Leslie MD, Hagedorn AN, Kodama EN, Marquez VE, Hughes SH, Mitsuya H, Parniak MA, Sarafianos SG.  2013.  Effects of substitutions at the 4′ and 2 positions on the bioactivity of 4′-ethynyl-2-fluoro-2′-deoxyadenosine.  Antimicrob Agents Chemother. 2013 Dec;57(12):6254-64. doi: 10.1128/AAC.01703-13. Epub 2013 Oct 7.
  19. Zhang W, Parniak MA, Mitsuya H, Sarafianos SG, Graebing PW, Rohan LC.  2013.  Preformulation studies of EFdA, a novel nucleoside reverse transcriptase inhibitor for HIV prevention.  Drug Dev Ind Pharm. 2013 Jul 10. [Epub ahead of print]
  20. Michailidis E, Ryan EM, Hachiya A, Kirby KA, Marchand B, Leslie MD, Huber AD, Ong YT, Jackson JC, Singh K, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG.  2013.  Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA.  Retrovirology. 2013 Jun 24;10:65. doi: 10.1186/1742-4690-10-65.
  21. Hachiya A, Reeve AB, Marchand B, Michailidis E, Ong YT, Kirby KA, Leslie MD, Oka S, Kodama EN, Rohan LC, Mitsuya H, Parniak MA, Sarafianos SG.  2013.  Evaluation of combinations of 4′-ethynyl-2-fluoro-2′-deoxyadenosine with clinically used antiretroviral drugs.  Antimicrob Agents Chemother. 2013 Jun 24. [Epub ahead of print]
  22. Shimane K, Kawaji K, Miyamoto F, Oishi S, Watanabe K, Sakagami Y, Fujii N, Shimura K, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN.  2013.  HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains. Antimicrob Agents Chemother. 2013 Aug;57(8):4035-8. doi: 10.1128/AAC.00237-13. Epub 2013 May 20.
  23. Adedeji AO, Severson W, Jonsson C, Singh K, Weiss SR, Sarafianos SG.  2013.  Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms.  J Virol. 2013 Jul;87(14):8017-28. doi: 10.1128/JVI.00998-13. Epub 2013 May 15.
  24. Xu HT, Colby-Germinario SP, Asahchop EL, Oliveira M, McCallum M, Schader SM, Han Y, Quan Y, Sarafianos SG, Wainberg MA.  2013.  Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine.  Antimicrob Agents Chemother. 2013 Jul;57(7):3100-9. doi: 10.1128/AAC.00348-13. Epub 2013 Apr 22.
  25. Ilina T, Labarge K, Sarafianos SG, Ishima R, Parniak MA.  2012.  Inhibitors of HIV-1 Reverse Transcriptase-Associated Ribonuclease H Activity.  Biology (Basel). 2012 Oct 19;1(3):521-41. doi: 10.3390/biology1030521.
  26. Rai DK, Schafer EA, Singh K, McIntosh MA, Sarafianos SG, Rieder E.  2013.  Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of foot-and-mouth disease virus in host cells.  Antiviral Res. 2013 Jun;98(3):380-5. doi: 10.1016/j.antiviral.2013.03.022. Epub 2013 Apr 8.
  27. Lee JH, Hachiya A, Shin SK, Lee J, Gatanaga H, Oka S, Kirby KA, Ong YT, Sarafianos SG, Folk WR, Yoo W, Hong SP, Kim SO.  2013. Restriction fragment mass polymorphism (RFMP) analysis based on MALDI-TOF mass spectrometry for detecting antiretroviral resistance in HIV-1 infected patients.  Clin Microbiol Infect. 2013 Jun;19(6):E263-70. doi: 10.1111/1469-0691.12167. Epub 2013 Mar 11.
  28. Izumi K, Kawaji K, Miyamoto F, Shimane K, Shimura K, Sakagami Y, Hattori T, Watanabe K, Oishi S, Fujii N, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN.  2013.  Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design.  Int J Biochem Cell Biol. 2013 Apr;45(4):908-15. doi: 10.1016/j.biocel.2013.01.015. Epub 2013 Jan 26.
  29. Tavis JE, Cheng X, Hu Y, Totten M, Cao F, Michailidis E, Aurora R, Meyers MJ, Jacobsen EJ, Parniak MA, Sarafianos SG.  2013.  The hepatitis B virus ribonuclease H is sensitive to inhibitors of the human immunodeficiency virus ribonuclease H and integrase enzymes.  PLoS Pathog. 2013 Jan;9(1):e1003125. doi: 10.1371/journal.ppat.1003125. Epub 2013 Jan 22.
  30. Michailidis E, Singh K, Ryan EM, Hachiya A, Ong YT, Kirby KA, Marchand B, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG.  2012.  Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.  Cell Mol Biol (Noisy-le-grand). 2012 Dec 22;58(1):187-95.
  31. Adedeji AO, Singh K, Sarafianos SG.  2012.  Structural and biochemical basis for the difference in the helicase activity of two different constructs of SARS-CoV helicase.  Cell Mol Biol (Noisy-le-grand). 2012 Dec 22;58(1):114-21.
  32. Ong YT, Kirby KA, Hachiya A, Chiang LA, Marchand B, Yoshimura K, Murakami T, Singh K, Matsushita S, Sarafianos SG.  2012.  Preparation of biologically active single-chain variable antibody fragments that target the HIV-1 gp120 V3 loop.  Cell Mol Biol (Noisy-le-grand). 2012 Dec 22;58(1):71-9.
  33. Singh K, Marchand B, Rai DK, Sharma B, Michailidis E, Ryan EM, Matzek KB, Leslie MD, Hagedorn AN, Li Z, Norden PR, Hachiya A, Parniak MA, Xu HT, Wainberg MA, Sarafianos SG. 2012. “Biochemical Mechanism of HIV-1 Resistance to Rilpivirine”. J Biol Chem, 2012 Nov 2;287(45):38110-23. doi: 10.1074/jbc.M112.398180. Epub 2012 Sep 6.
  34. Adedeji A, Singh K, Calcaterra N, Dediego M, Enjuanes L, Weiss S, Sarafianos SG. 2012. “Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase”. Antimicrob Agents Chemother 56(9), 4718-28.
  35. Murphey-Corb M, Rajakumar PA, Oluocj JK, Didier PJ, Reeve AB, Mitsuya H, Sarafianos SG, and Parniak M. (2012). “Response of SIV to the novel nucleoside reverse transcriptase 1 inhibitor 4′-2 ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) in vitro and in vivo”. Antimicrob Agents Chemother 56, 4707-12.
  36. Hachiya A, Marchand B, Kirby KA, Michailidis E, Tu X, Palczewski K, Ong YT, Li Z, Griffin DT, Schuckmann MM, Tanuma J, Oka S, Singh K, Kodama EN, Sarafianos SG.  2012.  “HIV-1 reverse transcriptase (RT) polymorphism 172K, suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and nonnucleoside RT inhibitors.” J Biol Chem, 287(35), 29988-99.
  37. Michailidis E, KirbyKA, HachiyaA, YooW, HongSP, KimSO, FolkWR, SarafianosSG. 2012. “Antiviral therapies: focus on Hepatitis B reverse transcriptase”. INVITED REVIEW Int J Biochem & Cell Biol 44,1060-71.
  38. Adedeji A, Marchand B, J te Velthius A, Snijder EJ, Weiss S, Eoff R, Singh K,Sarafianos SG*. 2012. “Mechanism of nucleic acid unwinding by SARS-CoV helicase; helicase activity enhancement by SARS-CoV RNA-dependent RNA-polymerase”. PLoS ONE 7(5):e36521. Epub 2012 May 15.
  39. KirbyK, Marchand B, OngYT, NdongweT, HachiyaA, Michailidis E, Leslie MD, SietsemaDV, FetterlyTL, DorstCA, Singh K, WangZ,  Parniak MA, and Sarafianos SG. 2012. “Structural and Inhibition Studies of the RNase H function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase.” Antimicrob Agents Chemother 56, 2048-61.
  40. Sohl CD, Singh K, Kasiviswanathan R, Copeland WC, Mitsuya H, Sarafianos SG, Anderson KS. 2011. “The mechanism of interaction of human mitochondrial DNA polymerase g with the novel nucleoside reverse transcriptase inhibitor 4’ethynyl-2-Fluoro-2’-deoxyadenosine indicates a low potential for host toxicity”. Antimicrob Agents Chemother 56(3), 1630-34.
  41. Ndongwe TP, Adedeji AO, Michailidis E, Ong YT, Hachiya A, Marchand B, Ryan EM, Rai DK, Kirby KA, Whatley AS, Burke DH, Johnson M, Ding S, Zheng YM, Liu SL, Kodama EI, Delviks-Frankenberry KA, Pathak VK, Mitsuya H, Parniak MA, Singh K, Sarafianos SG*. 2011. “Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase”. Nucleic Acids Res 40(1), 345-59.
  42. Michailidis E, Kirby K, Hachiya A, Yoo W, Hong SP, Kim S-O, Folk WR, Sarafianos SG. 2011. “Hepatitis B Virus genotypic differences map structurally close to NRTI resistance hot spots”. International Journal of Current Chemistry 2(4), 253-260.
  43. Izumi K, Watanabe K, Oishi S, Fujii N, Matsuoka M, Sarafianos SG, Kodama EN. 2011. “Potent anti-HIV-1 activity of N-HR-derived peptides including a deep-pocket-forming region without antagonistic effects on T-20”. Antivir Chem Chemother 22(1), 51-5.
  44. Ditzler MA, Bose D, Shkriabai N, Marchand B, Sarafianos SG, Kvaratskhelia M, Burke DH. 2011. “Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic natural substrates”.  Nucleic Acids Res 39(18), 8237-47.
  45. Kirby KA, Singh K, Michailidis E, Marchand B, Kodama EN, Ashida N, Mitsuya H, Parniak MA, Sarafianos SG.  2011.  “The sugar ring conformation of 4’-ethynyl-2-fluoro-2’-deoxyadenosine and its recognition by the polymerase active site of HIV reverse transcriptase.” Cell Mol Biol  57(1), 40-46.  PMCID: PMC3119259
  46. Hachiya A, Kodama EK, Schuckmann M, Kirby KA, Michailidis E, Sakagami Y, Oka S, Singh K, Sarafianos SG. 2011.  “K70Q adds high-level tenofovir resistance to “Q151M complex” HIV RT through the enhanced discrimination mechanism.” PLoS ONE 6(1), e16242.  PMCID:  PMC3020970.
  47. Durk R,SchaferE, MoranJ, SinghK, MarchandB, MichailidisE, AdeyemiY, PautlerC, Rodriguez L, McIntosh M, Rieder E, Sarafianos SG. 2010 “Inhibition of Foot and Mouth disease Virus RNA-dependent RNA polymerase.” PLoS ONE 5(12), e15049.  PMCID: PMC3006429.
  48. Shimura K, Nameki D, Kajiwara K, Watanabe K, Sakagami Y, Oishi S, Fujii N, Matsuoka M, Sarafianos SG, Kodama E. Resistance profiles of novel electrostatically constrained HIV-1 fusion inhibitors. J Biol Chem.280: 39471-80.  2010 Oct 11.
  49. Schuckmann MM, Marchand B, Hachiya A, Kodama EN, Kirby KA, Singh K, Sarafianos SG. The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. J Biol Chem. 285:39700-9.  2010 Sep 27.
  50. Tu X, Das K, Han Q, Bauman JD, Clark AD Jr, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos SG, Arnold E. Structural basis of HIV-1 resistance to AZT by excision. Nat Struct Mol Biol. 2010 Oct;17(10):1202-9. Epub 2010 Sep 19.PMID: 20852643
  51. Tebit DM, Lobritz M, Lalonde M, Immonen T, Singh K, Sarafianos S, Herchenröder O, Kräusslich HG, Arts EJ. Divergent evolution in reverse transcriptase (RT) of HIV-1 group O and M lineages: impact on structure, fitness, and sensitivity to nonnucleoside RT inhibitors. J Virol. 2010 Oct;84(19):9817-30. Epub 2010 Jul 14.PMID: 20631150
  52. Shimane K, Kodama EN, Nakase I, Futaki S, Sakurai Y, Sakagami Y, Li X, Hattori T, Sarafianos SG, Matsuoka M. Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4. Int J Biochem Cell Biol. 2010 Sep;42(9):1482-8. Epub 2010 May 16.PMID: 20580677
  53. Singh K, Marchand B, Kirby KA, Michailidis E, Sarafianos SG. Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase. Viruses. 2010 Feb 11;2(2):606-638.PMID: 20376302
  54. Abram ME, Sarafianos SG, Parniak MA. The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Retrovirology. 2010 Feb 1;7:6.PMID: 20122159
  55. Michailidis E, Marchand B, Kodama EN, Singh K, Matsuoka M, Kirby KA, Ryan EM, Sawani AM, Nagy E, Ashida N, Mitsuya H, Parniak MA, Sarafianos SG. Mechanism of inhibition of HIV-1 reverse transcriptase by 4′-Ethynyl-2-fluoro-2′-deoxyadenosine triphosphate, a translocation-defective reverse transcriptase inhibitor. J Biol Chem. 2009 Dec 18;284(51):35681-91. Epub .PMID: 19837673
  56. Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, Tu X, Clark AD Jr, Boyer PL, Hou X, Gaffney BL, Jones RA, Miller MD, Hughes SH, Arnold E. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J Biol Chem. 2009 Dec 11;284(50):35092-100. Epub 2009 Oct 7.PMID: 19812032
  57. Götte M, Rausch JW, Marchand B, Sarafianos S, Le Grice SF. Reverse transcriptase in motion: conformational dynamics of enzyme-substrate interactions. Biochim Biophys Acta. 2010 May;1804(5):1202-12. Epub 2009 Aug 7. Review.PMID: 19665597
  58. Hachiya A, Shimane K, Sarafianos SG, Kodama EN, Sakagami Y, Negishi F, Koizumi H, Gatanaga H, Matsuoka M, Takiguchi M, Oka S. Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naïve patients. Antiviral Res. 2009 Jun;82(3):115-21. Epub 2009 Feb 21.PMID: 19428602
  59. Naito T, Izumi K, Kodama E, Sakagami Y, Kajiwara K, Nishikawa H, Watanabe K, Sarafianos SG, Oishi S, Fujii N, Matsuoka M. SC29EK, a peptide fusion inhibitor with enhanced alpha-helicity, inhibits replication of human immunodeficiency virus type 1 mutants resistant to enfuvirtide. Antimicrob Agents Chemother. 2009 Mar;53(3):1013-8. Epub 2008 Dec 29.PMID: 19114674
  60. Izumi K, Kodama E, Shimura K, Sakagami Y, Watanabe K, Ito S, Watabe T, Terakawa Y, Nishikawa H, Sarafianos SG, Kitaura K, Oishi S, Fujii N, Matsuoka M. Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. J Biol Chem. 2009 Feb 20;284(8):4914-20.
  61. Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, Hughes SH, Arnold E. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J Mol Biol. 2009 Jan 23;385(3):693-713. Nov 3. Review.
  62. Sarafianos SG, Arnold E. Biochemistry. RT slides home… Science. 2008. Nov 14;322(5904):1059-60. No abstract available.
  63. Mukhopadhyay J, Das K, Ismail S, Koppstein D, Jang M, Hudson B, Sarafianos S, Tuske S, Patel J, Jansen R, Irschik H, Arnold E, Ebright RH. The RNA polymerase “switch region” is a target for inhibitors. Cell. 2008 Oct 17;135(2):295-307.
  64. Kawamoto A, Kodama E, Sarafianos SG, Sakagami Y, Kohgo S, Kitano K, Ashida N, Iwai Y, Hayakawa H, Nakata H, Mitsuya H, Arnold E, Matsuoka M. 2′-Deoxy-4′-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. Int J Biochem Cell Biol. 2008 Apr 11.
  65. Hachiya A, Kodama EN, Sarafianos SG, Schuckmann MM, Sakagami Y, Matsuoka M, Takiguchi M, Gatanaga H, Oka S. Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J Virol. 2008 Apr;82(7):3261-70.
  66. Boyer, PL, Sarafianos, SG, Clark, PK, Arnold E. and Huges, SH. Why do HIV-1 and HIV-2 use different pathways to develop AZT resistance? PLoS Pathog. 2006 Feb;2(2):e10. Epub 2006 Feb 17.
  67. Tuske S, Sarafianos SG, Wang X, Hudson B, Sineva E, Mukhopadhyay J, Birktoft JJ, Leroy O, Ismail S, Clark AD Jr, Dharia C, Napoli A, Laptenko O, Lee J, Borukhov S, Ebright RH, Arnold E. Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell. 2005 Aug 26;122(4):541-52.
  68. Sarafianos SG, Das K, Hughes SH, Arnold E. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases. Curr Opin Struct Biol. 2004 Dec;14(6):716-30. Review.
  69. Siddiqui MA, Hughes SH, Boyer PL, Mitsuya H, Van QN, George C, Sarafinanos SG, Marquez VE. A 4′-C-ethynyl-2′,3′-dideoxynucleoside analogue highlights the role of the 3′-OH in anti-HIV active 4′-C-ethynyl-2′-deoxy nucleosides. J Med Chem. 2004 Oct 7;47(21):5041-8.
  70. Sarafianos SG, Hughes SH, Arnold E. Designing anti-AIDS drugs targeting the major mechanism of HIV-1 RT resistance to nucleoside analog drugs. Int J Biochem Cell Biol. 2004 Sep;36(9):1706-15. Review.
  71. Tuske S, Sarafianos SG, Clark AD Jr, Ding J, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, Wang G, Gaffney BL, Jones RA, Jerina DM, Hughes SH, Arnold E. Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat Struct Mol Biol. 2004 May;11(5):469-74. Epub 2004 Apr 25.
  72. Xu X, Liu Y, Weiss S, Arnold E, Sarafianos SG, Ding J. Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res. 2003 Dec 15;31(24):7117-30.
  73. Sarafianos SG, Clark AD Jr, Das K, Tuske S, Birktoft JJ, Ilankumaran P, Ramesha AR, Sayer JM, Jerina DM, Boyer PL, Hughes SH, Arnold E. Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA. EMBO J. 2002 Dec 2;21(23):6614-24.
  74. Julias JG, McWilliams MJ, Sarafianos SG, Arnold E, Hughes SH. Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivo. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9515-20. Epub 2002 Jul 1.
  75. Tachedjian G, Orlova M, Sarafianos SG, Arnold E, Goff SP. Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type 1 reverse transcriptase. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7188-93.
  76. Boyer PL, Sarafianos SG, Arnold E, Hughes SH. Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase. J Virol. 2001 May;75(10):4832-42.
  77. Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E. Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 2001 Mar 15;20(6):1449-61.
  78. Boyer PL, Sarafianos SG, Arnold E, Hughes SH. Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3056-61.
  79. Sarafianos SG, Das K, Clark AD Jr, Ding J, Boyer PL, Hughes SH, Arnold E. Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10027-32.

Awards/Grants

  • 2014-today – Editorial Board “Journal of Biological Chemistry”
  • 2014-today – Reviewer, Veteran Administration Infectious Diseases A study section
  • 2013-today – Chancellor Excellence Chair in Molecular Virology, University of Missouri School of Medicine
  • 2013 – Chancellor’s Award for Outstanding Research and Creative Activity in the Biological Sciences
  • 2013 – Nominated for the Graduate Faculty Mentor Award, University of Missouri
  • 2012-today – Editorial Board “Antimicrobial Agents and Chemotherapy”
  • 2009 – Dorsett L Spurgeon MD Distinguished Medical Research Award for the most outstanding young faculty at the MU Medical School
  • 2009-2013 – Charter member of NIH AIDS AIDS Discovery and Development of Therapeutic Targets NIH Study section

Recent Patents

  1. World Intellectual Property Organization No. 10UMC015
    Dated: November 17 2011.
    Entitled: “Inhibitors of Foot-and-mouth-disease virus targeting the RNA-dependent polymerase activity of 3Dpol”.
  2. US Patent 13/919,951: Suppression of SARS, MERS and other coronavirus Replication by helicase inhibitors. 2013.
  3. Invention Disclosure: ”Inhibitors of SARS Coronavirus entry”. Submitted. 2013.

Research Awards

  1. Endowed chair, Chancellor’s Excellence Chair in Molecular Virology
  2. The Chancellor’s Award for Outstanding Research and Creative Activity in the Biological Sciences
  3. The Dorsett Spurgeon Distinguished Medical Research Award for most outstanding young faculty

Details on Research Funding Grants

  1. Endowed chair, Chancellor’s Excellence Chair in Molecular Virology
  2. The Chancellor’s Award for Outstanding Research and Creative Activity in the Biological Sciences
  3. The Dorsett Spurgeon Distinguished Medical Research Award for most outstanding young faculty

In the past eight years, after I joined MU, our research has been awarded with 31 grants (not including instrumentation proposals or fellowships for undergraduate students):

Total grants/fellowships awarded in the past 8 years: 31 – (another 2 R01 applications pending)

Total Costs awarded in the past 8 years: $15,542,950 – (another $5,642,083 is pending)

Total Direct Costs awarded in the past 8 years: $12,169,519 – (another $4,173,359 is pending)


  1. Sponsor: National Institutes of Health (NIH) R01AI121315
    Title: “Taking aim at HBV eradication using novel NRTIs and Capsid effectors”
    Role: Principal Investigator; 06/14/16 to 05/31/2021
  2. Sponsor: National Institutes of Health (NIH) R01GM118012
    Title: “Reverse Transcriptase Multi-Class Drug Resistance and Rilpivirine Susceptibility in Diverse HIV-1 Subtypes”
    Role: Principal Investigator; 07/01/16 to 05/31/2020
  3. Sponsor: National Institutes of Health (NIH) R01 AI120860-01
    Title: “Structural studies of HIV Capsid with host factors Capsid-targeting antivirals”
    Role: Principal Investigator. This is a multi-PI grant; 04/01/16 to 03/31/21
  4. Sponsor: National Institutes of Health (NIH) P50 GM103368
    Title: HIV macromolecular interactions and impact on viral evolution of drug resistance
    Role: Principal Investigator (PI Arthur Olson); 09/01/15 – 08/31/1705/01/15 to 04/30/19
  5. Sponsor: National Institutes of Health (NIH) R01 AI100890
    “Novel antivirals targeting the RNase H activity of HIV reverse transcriptase”
    Role: Principal Investigator. Trainee: Andrew Huber; 06/01/14 to 06/30/17
  6. Sponsor: National Institutes of Health (NIH) R01AI076119
    “Ultrapotent Inhibitors of Wild-type and Multi-drug Resistant HIV”
    Role: Principal Investigator. Trainee: graduate student Obiaara Ihenacho; 05/01/15 to 04/30/19
  7. Sponsor: National Institutes of Health (NIH) R01-AI076119
    Title: Ultrapotent inhibitors of wild-type and multi-drug resistant HIV
    Role: Principal Investigator, 04/01/14 to 03/31/19
  8. Sponsor: National Institutes of Health (NIH) R01 AI100890-01
    Title: Novel antivirals targeting the RNase H activity of HIV reverse transcriptase
    Role: Principal Investigator, This is a multi-PI grant; 07/01/12 to 06/30/17
  9. Sponsor: National Institutes of Health (NIH) R21 AI112417-01
    Title: Capsid-Targeting Small Molecules Blocking HIV through Novel Mechanism of Action
    Role: Principal Investigator 04/01/14 to 03/31/16
  10. Sponsor: National Institutes of Health (NIH) R01 AI099284-01
    Title: Hepatitis C antivirals: Mechanism of action, combination efficacy and resistance
    Role: Co-Investigator (PI: Charles Rice); 05/01/12 to 04/30/17
  11. Sponsor: Ministry of Health, welfare and Labor of Japan (Japanese Government)
    Title: Crystal structures of HBV reverse transcriptase
    Role: Principal Investigator, 01/01/2014-12/31/2014
  12. Sponsor: National Institutes of Health (NIH) P50 GM103368
    Title: HIV macromolecular interactions and impact on viral evolution of drug resistance
    Role: Principal Investigator (PI Arthur Olson); 05/01/13 – 04/30/14
  13. Sponsor: National Institutes of Health (NIH) R01 AI100890-01 diversity supplement
    Title: Novel antivirals targeting the RNase H activity of HIV reverse transcriptase
    Role: Principal Investigator (For Graduate Student Andrew Huber); 06/01/14 to 06/30/17
  14. Sponsor: Mizzou Advantage (University of Missouri)
    Title: Studying HIV-1 Subtype B or C Drug Resistance in Patient Cohorts from Missouri, Cameroon & India
    Role: Principal Investigator, 05/01/2014-04/30/2015
  15. Sponsor: National Institutes of Health (NIH) R21 AI094715
    Title: Structure-Based Expansion of Neutralization Ability of KD-247, an Anti-V3 mAb
    Role: Principal Investigator, 06/01/11 to 05/31/13
  16. Sponsor: National Institutes of Health (NIH) R01-AI076119
    Title: Ultrapotent inhibitors of wild-type and multi-drug resistant HIV
    Role: Principal Investigator, 07/01/2008 to 06/30/2013
  17. Sponsor: National Institutes of Health (NIH) American Recovery and Reinvestment Act of 2009 (ARRA) 3R01AI076119-02S1, Administrative supplement to R01-AI076119
    Title: Ultrapotent inhibitors of wild-type and multi-drug resistant HIV
    Role: Principal Investigator, 09/22/2009 to 08/31/2011
  18. Sponsor: NIH ARRA 3R01AI076119-01A2S1
    Title: Ultrapotent inhibitors of wild-type and multi-drug resistant HIV
    Role: Principal Investigator, 06/05/2009 to 09/30/2010
  19. Sponsor: NIH R01-AI074389
    Title: Determinates of anti-HIV nucleic acid aptamer potency and resistance
    Role: Co-Investigator (PI: Donald Burke), 02/01/2008 to 01/31/2013
  20. Sponsor: NIH R21: 1R21-AI079801
    Title: Microbicide properties of RT inhibitor combinations
    Role: Co-Investigator (PI: Michael Parniak), 07/01/2008 to 06/30/2010
  21. Sponsor: NIH R33: R33-AI079801
    Title: Microbicide properties of RT inhibitor combinations
    Role: Co-Investigator (PI: Michael Parniak), 09/01/2010-08/31/2013
  22. Sponsor: US Department of Agriculture-Agricultural Research Service (USDA-ARS)-58-1940-5-519
    Title: Program for prevention of animal infectious diseases: Advanced technologies for foreign animal disease vaccines and control
    Role: Principal Investigator (Program Director: Mark McIntosh), 01/01/2008 to 06/30/2012
  23. Sponsor: Trail to a Cure
    Title: Annual donation by the “Trail to a Cure” foundation for AIDS Research
    Role: Co-Principal Investigator, 2011-2013
  24. Sponsor: KOR-US, Korean Government
    Title: A Promising BINT (Bio, Information and Nano Technology)-Based Diagnostics/Theranostics Technology
    Role: Principal Investigator, 5/01/2009-4/30/2014
  25. Sponsor: TIBOTEC PHARMACEUTICALS, LTD, Belgium
    Title: Testing compounds for inhibition of human polymerases (Tibotec 2009)
    Role: Principal Investigator, 03/01/2009 to 02/28/2012
  26. Sponsor: Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (MRCE)-NIH grant
    Title: High-Throughput screening for inhibitors of Dengue virus and SARS coronavirus replicative enzymes
    Role: Principal Investigator, 0.6 mo. Dates: 03/01/2008 to 02/28/2009
  27. Sponsor: TIBOTEC PHARMACEUTICALS, LTD, Belgium
    Role: Principal Investigator, 02/01/2008 to 01/31/2009
  28. Sponsor: Genematrix Inc, Korea
    Title: Development of a biochip for prognosing treatment responses on multiple antivirals
    Role: Co-Investigator, (PIs: SunPyo Hong) 03/01/2007 to 02/28/2008
  29. Sponsor: USDA-ARS-58-1940-5-519
    Title: Program for prevention of animal infectious diseases: Advanced technologies for foreign animal disease vaccines and control
    Role: Principal Investigator, (Program Director: Mark McIntosh). 01/01/2007 to 06/30/2008
  30. Sponsor: University of Missouri: Missouri Advantage
    Title: Regional Symposium on Molecular Biophysics: Single‐Molecule Analysis of Macromolecules
    Role: Co-PI, (PI: Gerry Hazelbauer). 01/06/2010-12/30/2010
  31. Sponsor: Canadian Institutes of Health Research (CIHR)
    Title: Characterization of 4’-Ethynyl-2-Fluoro-2’-Deoxyadenosine, a Novel Translocation-Deficient Reverse Transcriptase Inhibitor
    Role: Sponsor, Post-doctoral fellowship for Dr. Bruno Marchand. 01/01/2010 to 2012
  32. Sponsor: American Foundation for AIDS Research (amFAR)
    Title: Inhibitors of wild-type and drug-resistant HIV reverse transcriptase
    Role: Sponsor, Post-doctoral fellowship for Dr. Bruno Marchand. 01/01/2008 to 12/31/2009
  33. Sponsor: University of Missouri Life Sciences Fellowship
    Title: Interactions between non-structural proteins of SARS
    Role: Sponsor, Post-doctoral fellowship for Dr. Bruno Marchand. 04/16/2007 to 04/15/2009 (discontinued on 01/01/2008 because of award of an overlapping fellowship)
  34. Sponsor: International Medical Center of Japan-AIDS Clinical Center
    Title: Mechanisms of HIV drug resistance
    Role: Sponsor, Post-doctoral fellowship support for Dr. Atsuko Hachiya; 7/1/09 to 6/30/1
  35. Sponsor: National Institutes of Health (NIH) F32AI009578-01A1, National Research Service Award
    Title: Structural studies of HIV reverse transcriptase in complex with RNA/DNA substrates
    Role: Recipient of post-doctoral fellowship (Mentor: Eddy Arnold), 05/09/1996 to 08/31/1999

Lab Members

Undergraduate Students

Lab Alumni

Robert RalstonDr. Rob Ralston (2011-2014) was a Research Assistant Professor who had worked for several years on Hepatitis C Virus in biotech and pharma, from early vaccine research at Chiron to small molecule research at Schering-Plough/Merck culminating in development of boceprevir, the first direct-acting antiviral approved for treatment of chronic hepatitis C. After work in Dr. Rice’s lab at The Rockefeller University, he moved to our lab and helped set up HCV virological assays and advanced microscopy techniques. He recently accepted a position as a Research Professor at the Kansas University Medical Center.


Eleftherios (Lefteris) MichailidisDr. Eleftherios (Lefteris) Michailidis (2006-2012) completed his Ph.D. in Molecular Microbiology and Immunology at the University of Missouri and was a postdoctoral fellow in my laboratory. His research was on the mechanism of EFdA, one of the most potent inhibitors of HIV, and on the discovery of novel inhibitors of Hepatitis B Virus. He published 17 papers while in our lab . He received the MU campus-wide Distinguished Dissertation Award for his doctoral thesis for the year 2012. Lefteris went on to continue his academic development as a postdoctoral fellow in Dr. Charles Rice’s laboratory (Rockefeller University) a leading scientist in virology of hepatitis C.


Bruno MarchandDr. Bruno Marchand (2007-2011); PhD in Microbiology from McGill University). He was awarded the prestigious and competitive amfAR Mathilde Krim fellowship (2008-2010); the competitive Canadian Institutes of Health post-doctoral award (for another 2.5 years); and the Life Sciences fellowship for distinguished post-docs. He gave oral presentations at important conferences including the 8th Ann Symp on Antiv Drug Resist (2008), two consecutive years at CROI (2009, 2010), the 9th Intr HIV Drug Resist Workshop (2009), the Intrn HIV and Hepatitis Viruses Drug Resist Workshop (Croatia, 2010), the Retroviruses meeting (Cold Spring Harbor, 2008), and at the Intersc Conf on Antimicrob Agents & Chem (ICAAC, Chicago 2007). He co-authored 18 manuscripts while in our lab. He was recruited by leader pharma company Gilead Sciences as a Research Scientist.


Yemi AdedejiDr. Adeyemi Adedeji (2007-2012), Doctor of Veterinary Medicine), completed his Ph.D. at the University of Missouri; in coronaviral replication and drug development with a GPA of 4.0 in 2012. Following his Ph.D he worked as a postdoctoral fellow in the lab for ~1year. He is a lead author of 9 manuscripts and also co-authored and additional 2 papers, 1 patent and one invention disclosure. He established SARS coronavirus (CoV)-related projects in the lab, including RNA synthesis (nsp12 RdRp), RNA unwinding (nsp13 helicase), and virus entry. He developed several assays, screened chemical libraries and discovered small molecule inhibitors of SARS-CoV entry and replication, which we have patented. Dr. Adedeji completed residency training in toxicologic pathology at the school of veterinary medicine, University of California-Davis (ranked as the #2 Veterinary School in the US). He is now a tenure-track faculty-Assistant Professor- at the College of Veterinary Medicine at Midwestern University, in Glendale, Arizona.


Dev RaiDr. Devendra Rai was a post-doctoral fellow in my lab from 2010 to 2012. During his time with my lab, Dr. Rai worked primarily on HIV resistance projects, as well as on the discovery and characterization of a Foot-and-Mouth Disease Virus (FMDV) antiviral. In fact, he went for additional training and work at the physically isolated USDA facility at Plum Island, NY, which is the highest Biosafety level facility for research on animal pathogens in this country. Dr. Rai co-authored 4 manuscripts in our laboratory. He went on to work at the USDA facility at Plum Island, NY.


Ademola KassimAdemola Kassim (2011-2013) was a MS graduate student from the Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford who conducted all of his research in our laboratory, where he worked for approximately two years. Ademola successfully defended his work in our lab on “Molecular Interactions of the nsp13 SARS-CoV Helicase with SSYA10-001 Helicase Inhibitor and the nsp12 SARS-CoV RNA-dependent RNA polymerase”. He has been a middle author of one published paper in 2014.


Ignacio de la Higuera HernandezIgnacio de la Higuera Hernández (Nacho), (2012) was a PhD graduate student from the Centro de Biología Molecular “Severo Ochoa” in Spain. His mentor, Dr. Esteban Domingo sent him to our lab for training on pre-steady state enzyme kinetics and to conduct experiments for his PhD thesis on the Foot-and-Mouth-Disease Virus 3D polymerase. Nacho’s data will be published in two manuscripts in two collaborative manuscripts with Dr. Domingo’s group.

 

 

Undergraduate Researchers

Ceili CornelisonCeili A. Cornelison (2009-2012) worked as an undergraduate researcher and as a technician in the lab, on the characterization of 3Dpol Foot-and-Mouth Disease Virus replicase. She is a coauthor of two papers from her work in the lab and graduated in 2014 with a BS on Computer Sciences .


Jacqueline CarricoJacqueline Carrico, BS Biochemistry, HONORS, Life Sciences Undergraduate Research Opportunity Program fellow. Coauthor in an upcoming publication (Marchand et al, 2014). Currently in the MD program at the University of Colorado School of Medicine. Also, HHMI fellowship, and she won the first prize for best Undergraduate research Thesis in the Department of Biochemistry.


Nicholas CalcaterraNicholas E. Calcaterra worked on identification of inhibitors of SARS-CoV helicase. He received a Life Sciences Undergraduate Research Opportunity Program (LSUROP) fellowship. He is a co-author in Adeyemi et al 2012, and is currently a graduate student at the Lieber Institute for Brain Development at Johns Hopkins University.


Daniel GriffinDaniel Griffin, BS Biochemistry, Discovery Program Fellow. Currently in the MD program at Saint Louis University. He was a coauthor of one manuscript (Hachiya et al, 2012).


Connor AbbottConnor Abbott was a Chemical Engineering undergraduate student who worked in the lab in 2012. He worked on protein expression and purification.


Leslie ChiangLeslie Chiang was an undergraduate researcher in biological Sciences and an HHMI fellow. She graduated with HONORS and also won the Jeanette and Herbert Fisher Prize and Endowment for Genetics Research in Biological Sciences among all Campus HONORS students. She worked with Yee Tsuey Ong on protein engineering of anti-HIV antibodies.


Paul ChoPaul Cho was a Biological Sciences undergraduate student who worked in the lab in 2012. He worked on protein expression and purification.


Jeremy ClincyJeremy Clincy was a Biochemistry major who worked in the lab in 2012. He was a McNair scholar.


Chris DorstChris Dorst was summer student from Washington University in St. Louis who came to the lab for two summers for undergraduate research. He is a coauthor in 3 manuscripts. Chris is in the science philosophy graduate program at the University of North Carolina Chapel Hill.


Tracy Fetterly
Tracy Fetterly was a summer student from Vanderbilt University who came to the lab for three summers for undergraduate research. She is a coauthor in three manuscripts. Tracy is currently in the Neuroscience Graduate Program at Vanderbilt University.


Katie LaddusawKatie Laddusaw was an undergraduate researcher in 2011 working with graduate student Yee Tsuey Ong on protein expression and purification.


Alan LeslieAlan Leslie BS in Biochemistry, EXPRESS student. He is currently employed at the biotech company ABC Labs in Columbia MO.


Max LeslieMax Leslie worked on the characterization of 3Dpol Foot-and-Mouth Disease Virus replicase. He is a co-author on a related paper (Durk et al, 2010). Max additionally worked on characterizing drug resistant mutants of HIV RT and XMRV and is a coauthor of 7 additional manuscripts. He was HHMI fellow in Spring 2011 and also an HONORS Biological Sciences student.


Kayla MatzekKayla Matzek was a Bryant Scholar in the lab (pre-accepted as a Medical Student at he University of Missouri School of Medicine. She worked for several years on pre-steady state kinetics characterizing drug resistant mutants of HIV RT and XMRV. Kayla was a coauthor of 3 manuscripts and is now in the MD program at the MU School of Medicine.


Jess NamJess Nam was an undergraduate researcher in 2012 working with Dr. Karen Kirby and Grace Yang on HIV reverse transcriptase expression and purification.


Yun PanYun Pan was an undergraduate researcher in 2012 working with graduate student Tanya Ndongwe on HCV-related projects.


Emily RyanEmily Ryan, Honors, Biological sciences, LSUROP fellow, co-author of 6 manuscripts and 12 presented posters. Selected to present her research to Missouri state legislators at Undergraduate Research Day at the Capitol, Jefferson City, MO in 2009 and 2010. She received the Thomas T. Strange Scholarship from MU College of Arts & Sciences, 2010. Also, in 2010 she received two undergraduate research awards: Molecular & Cellular Biology Honorable Mention and Life Sciences Honorable Mention. She is now studying osteopathic medicine at A.T. Still University in Kirksville, MO.


Hilary SchmidtHilary Schmidt is a senior biological engineering major who worked in the lab for 3 years as an HHMI fellow. She won the 2nd place undergraduate poster award for her work on the structure of HIV RT in complex with a novel RNase H inhibitor at the 2014 Institute of Biological Engineering Conference. She will be a coauthor on several upcoming manuscripts.


Daniel SietsmaDaniel Sietsema, BS Biological Sciences, coauthor in two publications (Kirby et al, 2012, Marchand et al, 2014). Dan is now a Research Assistant at the University of Colorado School of Medicine.


ArzooArzoo Singh Singh was a visiting scholar from India in Summer 2013.


Akki SinghAkki Singh was a visiting scholar from India in Summer 2013.