Anti-coronaviral Activity of Plant and Seaweed Secondary Metabolites: A Review

Background: Coronavirus Disease 2019 (COVID-19), one of the greatest challenges facing humanity, continues to affect millions of people worldwide. Vaccines approved and authorized for use are effective against COVID-19, but viral variants of concern may emerge in the near future. The discovery of novel antiviral agents will help humanity overcome COVID-19 and aid in any future viral pandemics. Objective(s): This review aimed to evaluate evidence from the plant-and seaweed-derived secondary com-pound-based interventions for viral diseases caused by coronaviruses. Method(s): A comprehensive search of several databases, including Cochrane Library, Web of Science and PubMed was conducted to identify available studies evaluating the outcomes of plant-and seaweed secondary metabolites in viral diseases such as Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome and COVID-19. Result(s): The volume of existing reports is irrefutable evidence that some plant-and seaweed-derived secondary compounds (e.g., mannose-specific lectins, griffithsin, cyanovirin-N, gallate, curcumin, luteo-lin, quercetin and betulinic acid) possess a potential antiviral ability against coronaviruses, including SARS-CoV-2. Conclusion(s): Plant and seaweed secondary metabolites with antiviral activity show their activity in different metabolic pathways. Besides reducing and preventing the metabolic damage caused by proinflamma-tory cytokines and oxidative stress, several plants and seaweed secondary metabolites can also be effective in improving some clinical indexes specific to COVID-19. Despite their effectiveness in preclinical studies, plant and seaweed-derived secondary compounds need more pharmacokinetic studies and safety measures concerning their mitogenic and allergenic properties.Copyright © 2022 Bentham Science Publishers.

Engineering recombinantly expressed lectin-based antiviral agents.

Cyanovirin-N (CV-N), a lectin from Nostoc ellipsosporum was found an infusion inhibitory protein for human immunodeficiency virus (HIV)-1. A tandem-repeat of the engineered domain-swapped dimer bound specific sites at hemagglutinin (HA), Ebola and HIV spike glycoproteins as well as dimannosylated HA peptide, N-acetyl-D-glucosamine and high-mannose containing oligosaccharides. Among these, CV-N bound the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein at a dissociation constant (KD) of 18.6 µM (and KD=260 µM to RBD), which was low-affinity carbohydrate-binding as compared with the recognition of the other viral spikes. Binding of dimannosylated peptide to homo-dimeric CVN2 and variants of CVN2 that were pairing Glu-Arg residues sterically located close to its high-affinity carbohydrate binding sites, was measured using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Binding affinity increased with polar interactions, when the mutated residues were used to substitute a single, or two disulfide bonds, in CVN2. Site-specific N-linked glycans on spikes were mediating the infection with influenza virus by broadly neutralizing antibodies to HA and lectin binding to HA was further investigated via modes of saturation transfer difference (STD)-NMR. Our findings showed that stoichiometry and the lectin's binding affinity were revealed by an interaction of CVN2 with dimannose units and either the high- or low-affinity binding site. To understand how these binding mechanisms add to viral membrane fusion we compare our tested HA-derived peptides in affinity with SARS-CoV-2 glycoprotein and review lectins and their mechanisms of binding to enveloped viruses for a potential use to simulate neutralization ability.

Discovery of a Natural Product with Potent Efficacy Against SARS-CoV-2 by Drug Screening.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed potent peptides against SARS-CoV-2 infection by carrying out MM-PBSA calculation based on the binding of 52 antiviral peptides (AVPs) to RBD. Considering the binding free energies of AVPs to RBD, cyanovirin-N (CV-N) showed the strongest RBD binding affinity among 52 AVPs. Upon structural analysis of RBD complex with CV-N, it was observed that 12 of the 13 key residues of RBD binding to ACE2 were hijacked by CV-N. CV-N bound to RBD at a smaller affinity of 14.9 nM than that of ACE2 and inhibited the recruitment of S1 to human alveolar epithelial cells. Further analysis revealed that CV-N suppressed SARS-CoV-2 S pseudovirion infection with a half-maximal inhibitory concentration (IC50) of 18.52 µg/mL. This study demonstrated a drug screening for AVPs against SARS-CoV-2 and discovered a peptide with inspiring antiviral properties, which provided a promising strategy for the COVID-19 therapeutic approach.

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.

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.