Discovery of Covalent Drugs Targeting the Key Enzymes of SARS-CoV-2 Using SCARdock

Abstract

Historically, covalent drugs were avoided in drug development process due to the possible toxicity linked to the covalent binding of such drugs and cellular proteins. However, recent years have witnessed the fast resurgence of the discovery of covalent drugs because of the realization of the advantages of covalent drugs in efficacy, duration of action, therapy-induced resistance, and targeting hard targets. Since December 2019, SARS-CoV-2 has caused nearly 40 million COVID-19 patients and over one million deaths in the whole world as of October 19, 2020. In contrast, effective drugs have not been found at the same time. Therefore, it is of great value to discover and design drugs for the prevention and cure of SARS-CoV-2 infection. Recently, we developed a simple but efficient method named as SCARdock for the discovery of covalent drugs. In this work, we present a detailed protocol of this method in discovering potential anti-SARS-CoV-2 drugs.