BACKGROUND

Despite the presence of SARS-CoV-2 antivirals, namely, remdesivir, nirmatrelvir and toremifene, these drugs entail adverse effects and limited effectiveness. Thus, development of a safer alternative is imperative, and likely candidates include the cell-free supernatant (CFS) and protein fractions from Lactiplantibacillus plantarum strains. These postbiotics have known antiviral properties primarily mediated by plantaricins and enhanced by organic acids.

The study determined the in silico mechanism of plantaricins against the receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), as well as compared the in vitro activities of the L. plantarum BS25 CFS, semi-purified and crude protein fractions, against the SARS-CoV-2 pseudotyped viruses (nCoV-S-EGFP) expressing the spike of wild-type (wt) Wuhan strain, Omicron BA.1 and BA.4/5 variants. Further, this study determined the metabolome of the strain BS25 CFS.

A quasi-experimental approach was utilized in the study. Plantaricins were screened for safety in silico, followed by molecular docking with RBD and ACE2. Using a cell culture model, two-fold dilutions of the CFS and fractions were tested for cytotoxicity and microneutralization against the pseudoviruses. Mass spectrometry was utilized for the metabolomics.

Plantaricins interact stably with RBD than ACE2 which were mediated by hydrogen, hydrophobic and covalent bonds. The activities of the CFS and fractions were substantially higher against the nCoV-SEGFP BA.4/5 variant. The 1:8 dilution of CFS entailed no cytotoxicity and displayed higher activities than toremifene. Metabolomics has identified a relatively abundant putative peptide, followed by organic acids and cyclic peptides.

Plantaricins can prevent SARS-CoV-2 entry by interacting with key RBD mutations or with intrinsically disordered RBD residues. The cationic and hydrophobic RBD mutations in the BA.4/5 variant may facilitate interactions with the putative peptide from the CFS and fractions, hence the observed potent activities. These findings can be used as basis for the development of an alternative antiviral targeting the RBD of live or pseudotyped SARS-CoV-2 variants.

Objective: This study aimed to determine the antiviral activity of ten Philippine medicinal plants against Zika virus (ZIKV). Methods: Lyophilized aqueous plant extracts were used for cell cytotoxicity and virus inhibition assays. The therapeutic index was computed from the 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) values. Plant metabolites were also identified using mass spectroscopy. An in-silico screening of these metabolites was done using ZIKV enzymes and the Axl protein in human microglial cells as target proteins, followed by the ranking of binding energy scores to generate a hypothesis on the possible mechanism of antiviral action. Results: The plants that demonstrated the highest therapeutic index were Momordica charantia, Psidium guajava, Vitex negundo, and Blumea balsamifera. The majority of the metabolites present in the aqueous extracts were saponin, terpenes and terpenoids, and anthocyanin. Further, in-silico docking results showed a higher binding affinity for viral replication proteins compared to the viral envelope protein. Conclusion The crude aqueous extracts of M. charantia, P. guajava, V. negundo, and B. balsamifera were the most potent candidate antiviral therapies against ZIKV among the ten plants tested. Meanwhile, the in-silico results suggested that the metabolites possibly employ an intracellular mechanism for the observed antiviral activity.
Herbal Medicine