Azadirachta indica A. Juss bark extract and its Nimbin isomers restrict β-coronaviral infection and replication

Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. The antiviral efficacy of Azadirachta indica bark extract (NBE) was assessed against SARS-CoV-2 and m-CoV-RSA59 infection. Effects of in vivo intranasal or oral NBE administration on viral load, inflammatory response, and histopathological changes were assessed in m-CoV-RSA59-infection. NBE administered inhibits SARS-CoV-2 and m-CoV-RSA59 infection and replication in vitro, reducing Envelope and Nucleocapsid gene expression. NBE ameliorates neuroinflammation and hepatitis in vivo by restricting viral replication and spread. Isolated fractions of NBE enriched in Nimbin isomers shows potent inhibition of m-CoV-RSA59 infection in vitro. In silico studies revealed that NBE could target Spike and RdRp of m-CoV and SARS-CoV-2 with high affinity. NBE has a triterpenoids origin that may allow them to competitively target panoply of viral proteins to inhibit mouse and different strains of human coronavirus infections, suggesting its potential as an antiviral against pan-β-Coronaviruses. [Display omitted] •What is already known:i.Azadirachta indica bark extract restricts HSV-1 and murine-β-Coronavirus replication, spread, and fusion in vitro.ii.m-CoV-MHV-A59/RSA59 when preincubated with Azadirachta indica bark extract (NBE) restricts viral infectivity in vivo.•What this study adds:i.NBE significantly restricts newly emerged human β-Coronavirus SARS-CoV-2 infection and replication in vitro.ii.Nimbin/Epinimbin significantly inhibits m-CoV-infectivity, cell-to-cell fusion, spread, and replication in vitro like NBE.•Clinical significance:i.NBE/it's isolated Nimbin/Epinimbin isomers significantly reduces coronaviral-induced clinical outcome, acute and chronic inflammatory pathology.ii.The Triterpenoids compounds of NBE inhibit SARS-CoV-2, HSV-1 and m-CoV infectivity, suggesting pan-β-anti-coronaviral/pan-antivirals.