The search for drugs to prevent or reduce the severity of human infection with SARS-CoV-1 or SARS-CoV-2 has centered on ones that are effective in treatment of human infections with other RNA viruses or in diminishing cytokine storms and other pathologies due to destructive host reactions. The interactions of a large number of these candidate drugs with their known viral and human protein targets are annotated, as are some drugs that inhibit Cytochrome P450 (CYP) oxidoreductases to prolong the plasma half-lives of antiviral drugs. In addition, effects of these drugs on unrelated essential human proteins, that might limit their use in vivo, are annotated.
A notable success of this search is a combination treatment, Paxlovid (NCT04960202), involving ritonavir, an inhibitor of CYP3A4 and CYP2B6 oxidoreductases, and nirmatrelvir, an inhibitor of SARS-CoV-2 3CLp protease, to block steps in maturation of viral replicase proteins (Hashemian et al. 2023).