CVC faculty leverage past success with new partnerships, technologies, and basic science discoveries in order to achieve high-impact translational outcomes:

Schinazi Lab

The primary interest of the Schinazi lab is to design and develop novel antiviral agents with the goal of advancing promising compounds to clinical trials. The group is developing novel small molecule inhibitors for the treatment of human viral infections including HIV, herpesviruses, hepatitis B and C, as well as emerging human viruses including Monkeypox, Dengue, West Nile, Yellow Fever, Chikungunya, Ebola, Norovirus and Enteroviruses. To complement drug discovery efforts, the group excels in the phenotypic and genotypic characterization of drug-resistant virus variants with the intention of mitigating resistance selection using drug combinations. Five antiviral agents developed in the Schinazi lab have gone on to advanced clinical studies resulting in 26 NDA approvals.

Kim Lab

Baek Kim's laboratory has been working on the molecular and cellular biology of HIV-1 replication, mutagenesis, evolution and viral escape for more than two decades. They do so by employing both biochemical and virological approaches. Their recent research focuses on HIV-1 infection to nondividing myeloid cells that serve as long-living HIV-1 reservoirs, contributing to HIV-1 persistence. They have found that HIV-1 replication in nondividing target cells harbors various distinct features, compared with activated CD4+ T cells. Their research claims differences between replication in these cell types in terms of host restriction, viral replication kinetics and cell biology/signaling responses can contribute to viral evolution and pathogenesis. Also, they recently launched a new anti-HIV drug discovery program through an industry collaboration, and this drug platform, called allosteric integrase inhibitors, targets HIV-1 integrase for its unique functions during both viral maturation and HIV-1 reactivation from latently infected T cell reservoirs.

Sarafianos Lab

The Sarafianos Laboratory works towards unraveling the molecular details of how biomedically-relevant enzymes function, how they are inhibited, how they develop drug resistance and towards developing drugs that will treat human disease by novel mechanisms of action. In pursuit of these goals, they use a combination of conventional and cutting-edge research tools, including protein biochemistry, molecular biology, fluorescence imaging/microscopy, macromolecular engineering, X-ray crystallography, molecular modeling, enzymology, and high-throughput technologies. Target proteins include HIV reverse transcriptase, HIV capsid protein, Hepatitis B virus (HBV) reverse transcriptase, and HBV capsid protein. Ongoing efforts focus on various steps of HIV, SARS, Mpox, Nipah HBV, and HCV life cycles, including cell entry, uncoating, reverse transcription, nuclear entry, assembly, and host interactions towards developing novel therapeutics.

Michailidis Lab

The Michailidis research program focuses on understanding the interaction between viruses and the host using a set of biochemical, cell-based and in vivo methods. In particular, the group is interested in HBV and the development of eradication strategies that involve state-of-the-art primary hepatocyte systems and humanized liver chimeric mice. These systems expand the scope of the research beyond viral hepatitis to other liver-related diseases and fields including fatty liver disease and liver immunometabolism. In addition, they have a strong interest in antiviral mechanisms carried out by interferon-stimulated genes and other host proteins but also small molecule inhibitors in regards to mechanisms of action and resistance. In this direction their main focus has been HIV, HBV, and SARS-CoV-2. To accomplish these goals, they use medium and high-throughput genetic screens (gene overexpression and CRISPR knockout) across different cell systems and in some cases in humanized mice.

2023

• Risener, C. J., Woo, S., Samarakoon, T., Caputo, M., Edwards, E., Klepzig, K., Applequest, W., Zandi, K., Goh, S. L., Downs-Bowen, J. A., Schinazi, R. F., Quave, C. L.: Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective.  Sci Rep 2023; 13(1):1244.  PMCID: PMC9868516.
• Biteau NG, Amichai SA, Azadi N, De R, Downs-Bowen J, Lecher JC, MacBrayer T, Schinazi RF, Amblard F. Synthesis of 4'-Substituted Carbocyclic Uracil Derivatives and Their Monophosphate Prodrugs as Potential Antiviral Agents. Viruses. 2023 Feb 16;15(2):544. doi: 10.3390/v15020544. PMID: 36851758; PMCID: PMC9962574.
• Cicka D, Niu Q, Qui M, Qian K, Miller E, Fan D, Mo X, Ivanov AA, Sarafianos SG, Du Y, Fu H. TMPRSS2 and SARS-CoV-2 SPIKE interaction assay for uHTS. J Mol Cell Biol. 2023 Mar 15:mjad017. doi: 10.1093/jmcb/mjad017. Epub ahead of print. PMID: 36921991.
• Lan S, Neilsen G, Slack RL, Cantara WA, Castaner AE, Lorson ZC, Lulkin N, Zhang H, Lee J, Cilento ME, Tedbury PR, Sarafianos SG. Nirmatrelvir Resistance in SARS-CoV-2 Omicron_BA.1 and WA1 Replicons and Escape Strategies. bioRxiv [Preprint]. 2023 Jan 3:2022.12.31.522389. doi: 10.1101/2022.12.31.522389. PMID: 36656782; PMCID: PMC9844013.
• Balasubramaniam A, Tedbury PR, Mwangi SM, Liu Y, Li G, Merlin D, Gracz AD, He P, Sarafianos SG, Srinivasan S. SARS-CoV-2 Induces Epithelial-Enteric Neuronal Crosstalk Stimulating VIP Release. Biomolecules. 2023 Jan 20;13(2):207. doi: 10.3390/biom13020207. PMID: 36830577; PMCID: PMC9953368.
• Singer MR, Dinh T, Levintov L, Annamalai AS, Rey JS, Briganti L, Cook NJ, Pye VE, Taylor IA, Kim K, Engelman AN, Kim B, Perilla JR, Kvaratskhelia M, Cherepanov P. The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function. mBio. 2023 Feb 28;14(1):e0356022. doi: 10.1128/mbio.03560-22. Epub 2023 Feb 6. PMID: 36744954; PMCID: PMC9973045.
• Lee D, Le Pen J, Yatim A, Dong B, Aquino Y, Ogishi M, Pescarmona R, Talouarn E, Rinchai D, Zhang P, Perret M, Liu Z, Jordan I, Elmas Bozdemir S, Bayhan GI, Beaufils C, Bizien L, Bisiaux A, Lei W, Hasan M, Chen J, Gaughan C, Asthana A, Libri V, Luna JM, Jaffré F, Hoffmann HH, Michailidis E, Moreews M, Seeleuthner Y, Bilguvar K, Mane S, Flores C, Zhang Y, Arias AA, Bailey R, Schlüter A, Milisavljevic B, Bigio B, Le Voyer T, Materna M, Gervais A, Moncada-Velez M, Pala F, Lazarov T, Levy R, Neehus AL, Rosain J, Peel J, Chan YH, Morin MP, Pino-Ramirez RM, Belkaya S, Lorenzo L, Anton J, Delafontaine S, Toubiana J, Bajolle F, Fumadó V, DeDiego ML, Fidouh N, Rozenberg F, Pérez-Tur J, Chen S, Evans T, Geissmann F, Lebon P, Weiss SR, Bonnet D, Duval X; CoV-Contact Cohort§; COVID Human Genetic Effort¶; Pan-Hammarström Q, Planas AM, Meyts I, Haerynck F, Pujol A, Sancho-Shimizu V, Dalgard CL, Bustamante J, Puel A, Boisson-Dupuis S, Boisson B, Maniatis T, Zhang Q, Bastard P, Notarangelo L, Béziat V, Perez de Diego R, Rodriguez-Gallego C, Su HC, Lifton RP, Jouanguy E, Cobat A, Alsina L, Keles S, Haddad E, Abel L, Belot A, Quintana-Murci L, Rice CM, Silverman RH, Zhang SY, Casanova JL. Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children. Science. 2023 Feb 10;379(6632):eabo3627. doi: 10.1126/science.abo3627. Epub 2023 Feb 10. PMID: 36538032

• New research collaboration between Emory and Pfizer aims to advance the discovery of antiviral agents for COVID-19
• Emory innovators step into the spotlight: Dr. Raymond Schinazi and colleagues receive the 2023 OTT "Deal of the Year" award
• B-HIVE Annual meeting will be held face to face on Monday, June 26th and Tuesday, June 27th at the NIH Natcher Conference Center in Bethesda, MD
• Hep-DART 2023 will be held on 3-7 December 2023 at Hacienda del Mar, Los Cabos, Mexico
• Baek Kim Named Schinazi Family Distinguished Professor in Biomedical Research