discovery of non-psychoactive scaffolds in Cannabis halting SARS-CoV-2 host entry and replication machinery.

Coronavirus disease still poses a global health threat which advocates continuous research efforts to develop effective therapeutics. We screened out an array of 29 cannabis phytoligands for their viral spike-ACE2 complex and main protease (M) inhibitory actions by modeling to explore their possible dual viral entry and replication machinery inhibition. Physicochemical and pharmacokinetic parameters (ADMET) formulating drug-likeness were computed. Among the studied phytoligands, cannabigerolic acid , cannabigerol , and its acid methyl ether possessed the highest binding affinities to SARS-CoV-hACE2 complex essential for viral entry. Canniprene , cannabigerolic methyl ether and cannabichromene were the most promising M inhibitors. These non-psychoactive cannabinoids could represent plausible therapeutics with added-prophylactic value as they halt both viral entry and replication machinery.