COViD-19 CoronavirusVirologist Andy Pekosz surveys some of the strategies in the works to stop SARS-CoV-2
COVID-19 Special Content

Science vs. Virus

Virologist Andy Pekosz surveys some of the strategies in the works to stop SARS-CoV-2.

By Brian W. Simpson • Infographics by Jennifer Fairman

Call it humanity’s revenge. The novel coronavirus—known for viciously exploiting victims’ weaknesses like hypertension and diabetes—is now having its own weaknesses targeted relentlessly. Andy Pekosz, PhD, a professor in Molecular Microbiology and Immunology, is investigating the virus to search out its vulnerabilities. An enthusiastic and precise scientist, Pekosz has deep research experience in how viruses like SARS and influenza interact with the respiratory epithelium—cells lining the upper airways that protect against dust particles, viruses, and other invaders. Here, he discusses the virus’s lifecycle, researchers’ strategies, and six targets. Spoiler alert: He’s optimistic.

 

Infection The virus enters the body through the nose, mouth, or eyes. It attaches to cells in the airway by binding to a protein called ACE-2. Internalization Binding to ACE-2 allows the virus to enter the cell via endocytosis. Protease Processing Cell enzymes called proteases causechanges to the virus’s spike protein so it isable to deliver viral RNA into the cell. Membrane Fusion & Release of Viral RNA Viral RNA is released intothe cell’s cytoplasm after the virus fuses membranes withthe cell. Th
  • Monoclonal antibodies & convalescent plasma

    Monoclonal antibodies & convalescent plasma

    Recovered patients have antibodies to SARS-CoV-2 in their blood plasma. Giving these antibodies to patients with active COVID-19 may be effective against the infection. They block the virus from binding to cells and may have other effects as well. They’re not a long-term fix, but they may help for a few weeks. Several companies are developing monoclonal antibodies for this same purpose.

  • Chloroquine & Hydroxychloroquine

    Chloroquine & Hydroxychloroquine

    These drugs appear to offer no significant benefits—but have increased risk. They were shown to have great efficacy in laboratory settings, but that hasn’t translated to an effective drug for humans. That’s something that happens a lot, actually. Plus, drug trials have shown there is a risk for heart arrhythmia and other heart issues.

  • ACE-2 inhibitors

    ACE-2 inhibitors

    The advantage or disadvantage of drugs called ACE-2 inhibitors is not entirely clear for COVID-19 infections. Targeting the ACE-2 with antibodies or using “decoy” ACE-2 molecules has the potential to inhibit virus entry in ways similar to antibodies.

  • Inhibit protease activity

    Inhibit protease activity

    It may be that the best antiviral drugs will come from drugs that target the virus’s proteases, but they are a long-term project. Proteases are enzymes that perform essential functions for the virus, so if you stop them, you stop the virus. Medicinal chemists love these because they work all the time and have lots of spaces that drugs can be designed to target. 

  • Inhibiting RNA polymerase

    Inhibiting RNA polymerase

    RNA polymerase is another enzyme that SARS-CoV-2 needs to replicate. The drug favipiravir has been shown to be effective in shortening and clearing the infection, as has the better-known remdesivir. Both have been tested extensively in humans because they have activity against multiple classes of viruses, not just coronaviruses.

  • Vaccines

    Vaccines

    Vaccines could be the ultimate solution to COVID-19. A future vaccine will help the body generate antibodies that target the SARS-CoV-2 virus and prevent it from infecting human cells. More than 100 different candidates are in the works. Vaccines should come on board faster than we’ve ever seen before, but they still have to go through all the safety testing and efficacy trials.