From quantum-derived principles underlying cysteine reactivity to combating the COVID-19 pandemic.

ABSTRACT: The COVID-19 pandemic poses a challenge in coming up with quick and effective means to counter its cause, the SARS-CoV-2. Here, we show how the key factors governing cysteine reactivity in proteins derived from combined quantum mechanical/continuum calculations led to a novel multi-targeting strategy against SARS-CoV-2, in contrast to developing potent drugs/vaccines against a single viral target such as the spike protein. Specifically, they led to the discovery of reactive cysteines in evolutionary conserved Zn²⁺-sites in several SARS-CoV-2 proteins that are crucial for viral polypeptide proteolysis as well as viral RNA synthesis, proofreading, and modification. These conserved, reactive cysteines, both free and Zn²⁺-bound, can be targeted using the same Zn-ejector d

SUBMITTER: Mazmanian K 

PROVIDER: S-EPMC9111396 | biostudies-literature | 2022 Sep-Oct

REPOSITORIES: biostudies-literature