Stuart M. Weston, PhD

• University College London, UK, B.SC. Biomedical Sciences, 2009-2012
• MRC Laboratory for Molecular Cell Biology, University College London, UK, PhD, 2012-2016
• University of Maryland School of Medicine, Post-doctoral fellow in the lab of Matthew Frieman, 2016-2021

The main focus of my research is centered around developing a better understanding of how a virus interacts with the host cells it infects, with a view towards leveraging this knowledge for the development of antiviral drugs. The COVID-19 pandemic helped to highlight the level to which we are under-prepared for rapidly emerging pathogenic viruses. While the pandemic has seen incredible speed of vaccine development, effective antiviral drugs are still lacking.

The traditional approach to the development of antivirals has been limited by two features, firstly the chemicals that are approved for use target the virus which can allow for the evolution of antiviral-resistance. Secondly, we are faced with a problem of one-drug-one-bug where by antivirals developed only target a specific virus, and do not have the potential for broad usage akin to antibiotics for the treatment of bacterial infection. By studying virus-host interactions, we hope to be able to find host-directed antiviral drug targets which would limit the potential for viral evolution to become resistant, and has the potential to be more broad acting against multiple viruses.

The development of broad acting antivirals would situate us much better to deal with novel pathogens. The viruses I spend the most time researching are those with the potential to be pandemic pathogens due to their respiratory spread, these being influenza virus and coronaviruses. Utilizing a yeast-based screening system we have identified the SKI complex as a potential target for such a broad-spectrum antiviral approach. The SKI complex is a cellular protein complex that is involved with RNA metabolism. We have identified that the complex is important for the replication of influenza virus and coronaviruses. We have developed chemicals to target the complex and these show antiviral activity again influenza, coronaviruses and the filoviruses Ebola and Marburg. The ongoing research is aimed at defining what role the SKI complex plays in the replication of this broad array of viruses and pushing the development of antiviral chemicals.

Coronavirus, COVID-19, SARS-CoV, SARS-CoV-2, MERS-CoV, influenza, antiviral drugs, host factors.

• Weston S, Baracco L, Keller C, Matthews K, McGrath ME, Logue J, Liang J, Dyall J, Holbrook MR, Hensley LE, Jahrling PB, Yu W, MacKerell AD Jr, Frieman MB. The SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses. Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30687-30698.
• Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, Reyes HM, Weiss SR, Frieman MB. Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo. J Virol. 2020 Oct 14;94(21):e01218-20.
• Weston S, Matthews KL, Lent R, Vlk A, Haupt R, Kingsbury T, Frieman MB. A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication. J Virol. 2019 Jul 30;93(16):e00197-19.
• Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H, Smith G, Patel N, Frieman MB, Haupt RE, Logue J, McGrath M, Weston S, Piedra PA, Desai C, Callahan K, Lewis M, Price-Abbott P, Formica N, Shinde V, Fries L, Lickliter JD, Griffin P, Wilkinson B, Glenn GM. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020 Dec 10;383(24):2320-2332.
• Martin-Sancho L, Lewinski MK, Pache L, Stoneham CA, Yin X, Becker ME, Pratt D, Churas C, Rosenthal SB, Liu S, Weston S, De Jesus PD, O'Neill AM, Gounder AP, Nguyen C, Pu Y, Curry HM, Oom AL, Miorin L, Rodriguez-Frandsen A, Zheng F, Wu C, Xiong Y, Urbanowski M, Shaw ML, Chang MW, Benner C, Hope TJ, Frieman MB, García-Sastre A, Ideker T, Hultquist JF, Guatelli J, Chanda SK. Functional landscape of SARS-CoV-2 cellular restriction. Mol Cell. 2021 Jun 17;81(12):2656-2668.e8