Potent SARS-CoV-2 Direct-Acting Antivirals Provide an Important Complement to COVID-19 Vaccines

摘要

I n just the past seven years, the world has experienced three major pandemics, all stemming from different viruses, namely, the Ebola virus, the Zika virus, and the SARSCoV-2 virus. Of these, COVID-19 (caused by the SARS-CoV-2 virus) has been by far the most devastating, with deaths and illnesses that now approach those observed during the first year of the 1918 Spanish flu pandemic. The early stages of COVID-19 infection are dominated by host cell invasion mediated by binding of the SARS-CoV-2 S protein to cells containing the angiotensin-converting enzyme 2 (ACE2) surface receptor protein. While in COVID-19, the primary infection occurs on the tiny air sacs in the lungs (alveoli), the ACE2 protein is ubiquitous to many human tissues, and this can result in additional sites of infection. Although some infected patients remain asymptomatic throughout the course of the disease, most begin to exhibit symptoms within 5?7 days after being infected, and a subset of those progress to a variety of severe symptoms (e.g., difficulty breathing (dyspnea), low oxygen (hypoxia)) or even critical symptoms (e.g., respiratory failure, shock, or multiorgan dysfunction) brought on by an immune-mediated inflammatory response. To combat this effectively, we clearly need drugs to treat infected individuals1 and vaccines to protect uninfected individuals.