Carvacrol: A PL^pro Inhibitor of SARS-CoV-2 is a Natural Weapon for COVID-19

The outbreak of SARS-CoV-2 creates the biggest crisis to human health and adversely affects the economic growth worldwide. Recently, several vaccines have been emerged by the manufacturers to combat COVID-19. Unfortunately, no therapeutic medication has yet been approved by FDA for the treatment of this disease. In this aspect, several research groups have paid attention to find out the potential SARS-CoV-2 protein inhibitors from the bio-molecules available in medicinal plants, spices, and vegetables. In this paper, we have performed the structure-based virtual screening (VS) of 120 compounds derived from Nigella sativa (NS) against M^pro, PL^pro and Spike proteins of SARS-CoV-2. Strong binding interactions of M^pro occurred with hits NS-40, and NS-84 whereas hits NS-72D and NS-95D showed strong binding interaction with Spike protein. Interestingly, four promising hits namely NS-21, NS-40, carvacrol and menthol exhibited good binding interactions with both M^pro and Spike proteins. It was observed that carvacrol, a monoterpenoid phenol exhibited several biological activities, has favourable binding affinity towards papain-like protease of SARS-CoV-2. This small molecule may be used as a natural weapon to combat the COVID-19.