Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

Abstract

The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (−16.8 ± 0.02 kcal/mol, −12.3 ± 0.03 kcal/mol and −13.4 ± 0.02 kcal/mol, respectively) with the spike protein, the main protease (Mpro) and the papainlike protease (PLpro) of SARS-CoV-2. Cyanovirin-N was observed to interact with the crucial residues involved in the attachment of the human ACE2 receptor. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) approach revealed that all forms of energy, except the polar solvation energy, favourably contributed to the interactions of cyanovirin-N with the viral proteins. With particular emphasis on cyanovirin-N, the current work presents evidence for the potential inhibition of SARS-CoV-2 by cyanobacterial proteins, and offers the opportunity for in vitro and in vivo experiments to deploy the cyanobacterial proteins as valuable therapeutics against COVID-19.

Potential Inhibitors Targeting Papain-Like Protease of SARS-CoV-2: Two Birds With One Stone

“…Actually, “Xuebijing”, a complex traditional Chinese preparation consisting of Salvia miltiorrhiza, has been included in the Chinese clinical treatment strategy for COVID-19 and reduces multiple organ damage through anti-inflammation and improving immune function ( Tong et al, 2020 ). Other natural compounds, such as EGCG (a Green Tea Catechin) ( Chourasia et al, 2021 ), cyanovirin-N ( Naidoo et al, 2021 ), several Terpene compounds ( Diniz et al, 2021 ), and propolis derivatives ( Yosri et al, 2021 ), were also extensively studied in molecular simulations and exhibited high binding affinities with SARS-CoV-2 PLpro. But further in vitro and in vivo studies are needed to verify their potential.…”

An insight into SARS-CoV-2 structure, pathogenesis, target hunting for drug development and vaccine initiatives

“…No in vitro or in vivo study against PLpro has been found during the preparation of this manuscript but several in silico studies have been performed in search of potential compounds against PLpro. 133–136…”

“…[130][131][132] No in vitro or in vivo study against PLpro has been found during the preparation of this manuscript but several in silico studies have been performed in search of potential compounds against PLpro. [133][134][135][136] 7.1.2.2 RdRp. RdRp is the most crucial enzyme in the RNA virus family as it mediates the transcription and replication of the RNA genome during infection which facilitates the chance to use it as a drug target.…”

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins

“…In the scientific literature, there is perhaps the only serious attempt to assess the binding affinity of CV-N and SVN to the S-protein of SARS-CoV-2 using the methods of molecular mechanics and the solution of the Poisson-Boltzmann equation (MM/PBSA -molecular mechanics/Poisson-Boltzmann surface area). She showed the prospect of studying these lectins as new drugs, dietary supplements and functional foods [37].…”

“…Вместе с тем, этому подходу уделяется недостаточное внимание. В научной литературе имеется, пожалуй, единственная серьёзная попытка оценить аффинность связывания CVN и SVN по отношению к S-белку SARS-CoV-2 с помощью методов молекулярной механики и решения уравнения Пуассона-Больцмана (MM/PBSA -molecular mechanics/Poisson-Boltzmann surface area), которая продемонстрировала перспективность изучения этих лектинов в качестве новых лекарств, БАД и продуктов функционального питания [37].…”