The in-silico potential of Andrographis paniculata phytocompounds as antiviral for the treatment of COVID-19: A systematic review

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19), many studies have been conducted to develop definitive therapeutic agents for this viral disease. The in-silico method has become the best solution for the initial step in discovering potential antiviral compounds. Several phytocompounds from a medicinal plant, Andrographis paniculata, were reported to have activity inhibiting SARS-CoV-2 proteins. The present systematic review aims to determine the potency of A. paniculata compounds against COVID-19. We undertook a systematic search in two databases, PubMed and Google Scholar, and included original articles that applied in-silico methods for phytocompounds of A. paniculata in COVID-19. Twenty-nine original articles were included in the systematic review. We report that 50 of the 107 A. paniculata phytocompounds (46.73%) were against SARS-CoV-2. We found that five protein targets of SARS-CoV-2 are highly conserved structures mostly used in the articles, which are main protease, papain-like protease, RNA-dependent RNA polymerase, Nsp15, and spike protein. Six A. paniculata phytocompounds have an inhibition activity of those five protein targets including andrographolide, neoandrographolide, isoandrographolide, 14-deoxyandrographolide, 14-deoxy-11,12-didehydroandrographolide, and andrographidin C as main diterpenoid compounds. Based on the literature evidence, some of the A. paniculata phytocompounds could be potential antiviral agents due to their strong binding affinities and stable conformations toward SARS-CoV-2 proteins.

Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2

“…Eurycoma harmandiana, Sophora avescens and Andrographis paniculata contain phyto-compounds, such as terpenoids, avonoids and their glycosides, act against SARS-COV-2 PLpro and Mpro proteases. 80,173,182 A combined approach for in silico screening towards repositioning of FDA-approved drug candidates for anticoronaviral therapy has identied Ouabain, which is an antiarrhythmic drug of plant origin, as a dual inhibitor for both PLpro and Mpro enzymes. 183 Using in vitro studies and in silico screening, it has been shown that some purine nucleosides inhibiting nucleoside phosphorylase enzymes, such as Forodesine and Riboprine, revealed strong repurposing potential against two broadly conserved SARS-CoV-2 enzymes, such as RNA-dependent RNA polymerase (RdRp) and 3 ′ -to-5 ′ exoribonuclease (ExoN), irrespective of the SARS-CoV-2 variant type (Fig.…”

“…Eurycoma harmandiana , Sophora flavescens and Andrographis paniculata contain phyto-compounds, such as terpenoids, flavonoids and their glycosides, act against SARS-COV-2 PLpro and Mpro proteases. 80,173,182…”

“…Recent trends in the drug design against COVID-19 are focused on developing multi-target inhibitors for ghting several crucial proteins of SARS-CoV-2 with high potency. 167,[170][171][172][173][174] The ability to identify inhibitors with dual inhibition against both Mpro and PLpro will increase the chances of success in the development of drug molecules against new variants of SARS-CoV-2. 53,[175][176][177][178] Some studies have already reported compounds identied as dual-acting SARS-CoV-2 protease inhibitors that target both Mpro and PLpro (Fig.…”