Virus World

Over four years have passed since the beginning of the COVID-19 pandemic. The scientific response has been rapid and effective, with many therapeutic monoclonal antibodies and small molecules developed for clinical use. However, given the ability for viruses to become resistant to antivirals, it is perhaps no surprise that the field has identified resistance to nearly all of these compounds. Here, we provide a comprehensive review of the resistance profile for each of these therapeutics. We hope that this resource provides an atlas for mutations to be aware of for each agent, particularly as a springboard for considerations for the next generation of antivirals. Finally, we discuss the outlook and thoughts for moving forward in how we continue to manage this, and the next, pandemic.

Published (April 18, 2024):

https://doi.org/10.1016/j.chembiol.2024.03.008

The scientist who helped successfully combat the HIV/AIDS epidemic explains the science behind the novel coronavirus and looks toward the future of the world affected by COVID-19. As of March 20, more than 8,700 people worldwide had died of COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Caltech trustee David Ho (BS '74) of the Aaron Diamond AIDS Research Center, Columbia University, says that this is just the tip of the iceberg. Ho, an expert on viral epidemics, has spent decades researching HIV/AIDS, having begun his career in Los Angeles, "ground zero" of the first outbreak, in the early 1980s. On March 18, Ho sat down with members of the Caltech community to discuss the novel coronavirus and the future of our society in the light of this global pandemic.

Walk us through the spread of the virus in the United States. What does the country look like right now?

Let me just give you a picture of what I see here in New York. About two weeks ago, we had our initial case, and now in New York City newly diagnosed confirmed cases are tripling every two days. In our New York Presbyterian Hospital, approximately 25 percent of the swab samples that are submitted for testing are positive. In the suburban communities outside of New York, approximately 10 percent of the swabs submitted are positive. So, the virus is everywhere. And in New York, we know that we are in the exponential growth phase of the epidemic.

Looking back at what has transpired throughout the world, we saw the first wave hit China; the second wave hit South Korea, Italy, and Iran; and then, trailed by only about a week or so, France, Germany, Spain, and the U.S. We all know that China went through a period of great devastation. It has over 80,000 cases. Italy is rapidly catching up, with over 31,000 cases. We suspect that in the U.S. this will rapidly sweep from the coastal regions and it will hit middle America. It is already there, but we will see exponential growth very, very soon. Then of course we are all worried about what would happen when this epidemic strikes places like Africa and India where the health care system is less developed.....

Scientists have identified a diverse group of antibodies that block the new coronavirus’s ability to infect cells — even when applied in low doses. The immune-system proteins called neutralizing antibodies interfere with hostile microbes trying to enter target cells. David Ho at Columbia University Vagelos College of Physicians and Surgeons in New York City and his colleagues studied neutralizing antibodies from the plasma of five people with severe cases of COVID-19 (L. Liu et al. Nature http://doi.org/d4md; 2020).

Nineteen antibodies proved highly effective at preventing SARS-CoV-2 infection of cell samples. A small dose of one of the antibodies protected golden Syrian hamsters (Mesocricetus auratus) from SARS-CoV-2 infection. The 19 antibodies attach to a variety of locations on the coronavirus spike protein. A therapy made from antibodies that fasten onto the spike protein at multiple sites could be difficult for the virus to evade through mutation..

Original Study Published in Nature (July 22, 2020):

https://doi.org/10.1038/s41586-020-2571-7