Potential inhibitors and plant based technology: An alternative approach to treat corona virus.

The current pneumonia outbreak, which began in early December 2019 near Wuhan City, Hubei Province, China, is caused by a novel corona virus (CoV) known as '2019-nCoV' or '2019 novel corona virus or COVID-19' by the World Health Organization (WHO). Vaccines are available to prevent corona virus contagious infection or to reduce the viral load in body but virus is continuously mutating itself to infect people at severity. In this critical scenario this review provide a compiled study for techniques and tools that can be used to treat corona virus infections and its variants by some modern techniques and natural products such as inhibitors, siRNA technique and plant based approaches. This review focuses on healthy treatment and strategies that can be used effectively to treat the disease globally by reducing the post COVID symptoms.

ADMET profile and virtual screening of plant and microbial natural metabolites as SARS-CoV-2 S1 glycoprotein receptor binding domain and main protease inhibitors.

In an attempt to search for selective inhibitors against the SARS-CoV-2 which caused devastating of lives and livelihoods across the globe, 415 natural metabolites isolated from several plants, fungi and bacteria, belonging to different classes, were investigated. The drug metabolism and safety profiles were computed in silico and the results showed seven compounds namely fusaric acid, jasmonic acid, jasmonic acid methyl ester, putaminoxin, putaminoxin B and D, and stagonolide K were predicted to having considerable absorption, metabolism, distribution and excretion parameters (ADME) and safety indices. Molecular docking against the receptor binding domain (RBD) of spike glycoprotein (S1) and the main protease (Mpro) exposed the compounds having better binding affinity to main protease as compared to the S1 receptor binding domain. The docking results were compared to an antiviral drug penciclovir reportedly of clinical significance in treating the SARS-CoV-2 infected patients. The results demonstrated the test compounds jasmonic acid, putaminoxins B and D bound to the HIS-CYS catalytic dyad as well as to other residues within the MPro active site with much greater affinity than penciclovir. The findings of the study suggest that these compounds could be explored as potential SARS-CoV-2 inhibitors, and could further be combined with the experimental investigations to develop effective therapeutics to deal with the present pandemic.

From Fighting Critters to Saving Lives: Polyphenols in Plant Defense and Human Health.

Polyphenols, such as flavonoids and phenolic acids, are a group of specialized metabolites in plants that largely aid in plant defense by deterring biotic stressors and alleviating abiotic stress. Polyphenols offer a wide range of medical applications, acting as preventative and active treatments for diseases such as cancers and diabetes. Recently, researchers have proposed that polyphenols may contribute to certain applications aimed at tackling challenges related to the COVID-19 pandemic. Understanding the beneficial impacts of phytochemicals, such as polyphenols, could potentially help prepare society for future pandemics. Thus far, most reviews have focused on polyphenols in cancer prevention and treatment. This review aims to provide a comprehensive discussion on the critical roles that polyphenols play in both plant chemical defense and human health based on the most recent studies while highlighting prospective avenues for future research, as well as the implications for phytochemical-based applications in both agricultural and medical fields.

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12.

Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). In this study, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomesNsp12Nsp13). Mechanistically, we show that exosomesNsp12Nsp13 are taken up by lung macrophages, leading to activation of nuclear factor κB (NF-κB) and the subsequent induction of an array of inflammatory cytokines. Induction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß from exosomesNsp12Nsp13-activated lung macrophages contributes to inducing apoptosis in lung epithelial cells. Induction of exosomesNsp12Nsp13-mediated lung inflammation was abolished with ginger exosome-like nanoparticle (GELN) microRNA (miRNA aly-miR396a-5p. The role of GELNs in inhibition of the SARS-CoV-2-induced cytopathic effect (CPE) was further demonstrated via GELN aly-miR396a-5p- and rlcv-miR-rL1-28-3p-mediated inhibition of expression of Nsp12 and spike genes, respectively. Taken together, our results reveal exosomesNsp12Nsp13 as potentially important contributors to the development of lung inflammation, and GELNs are a potential therapeutic agent to treat COVID-19.

Secondary Metabolites of Plants as Modulators of Endothelium Functions.

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

Plant-Based Vaccines: The Way Ahead?

Severe virus outbreaks are occurring more often and spreading faster and further than ever. Preparedness plans based on lessons learned from past epidemics can guide behavioral and pharmacological interventions to contain and treat emergent diseases. Although conventional biologics production systems can meet the pharmaceutical needs of a community at homeostasis, the COVID-19 pandemic has created an abrupt rise in demand for vaccines and therapeutics that highlight the gaps in this supply chain's ability to quickly develop and produce biologics in emergency situations given a short lead time. Considering the projected requirements for COVID-19 vaccines and the necessity for expedited large scale manufacture the capabilities of current biologics production systems should be surveyed to determine their applicability to pandemic preparedness. Plant-based biologics production systems have progressed to a state of commercial viability in the past 30 years with the capacity for production of complex, glycosylated, "mammalian compatible" molecules in a system with comparatively low production costs, high scalability, and production flexibility. Continued research drives the expansion of plant virus-based tools for harnessing the full production capacity from the plant biomass in transient systems. Here, we present an overview of vaccine production systems with a focus on plant-based production systems and their potential role as "first responders" in emergency pandemic situations.

In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis.

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

High stability of plant-expressed virus-like particles of an insect virus in artificial gastric and intestinal fluids.

The harsh conditions of the gastro-intestinal (GI) milieu pose a major barrier to the oral delivery of protein nanocages. Here we studied the stability of Nudaurelia capensis omega virus (NωV) virus-like particles (VLPs) in simulated GI fluids. NωV VLPs capsids and procapsids were transiently expressed in plants, the VLPs were incubated in various simulated GI fluids and their stability was determined by gel electrophoresis, density gradient ultracentrifugation and transmission electron microscopy (TEM). The results showed that the capsids were highly resistant to simulated gastric fluids at pH ≥ 3. Even under the harshest conditions, which consisted of a pepsin solution at pH 1.2, NωV capsids remained assembled as VLPs, though some digestion of the coat protein occurred. Moreover, 80.8% (±10.2%) stability was measured for NωV capsids upon 4 h incubation in simulated intestinal fluids. The high resistance of this protein cage to digestion and denaturation can be attributed to its distinctively compact structure. The more porous form of the VLPs, the procapsid, was less stable under all conditions. Our results suggest that NωV VLPs capsids are likely to endure transit through the GI tract, designating them as promising candidate protein nanocages for oral drug delivery.

Genomics approaches to synthesize plant-based biomolecules for therapeutic applications to combat SARS-CoV-2.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is devastative to the humankind for which neither vaccines nor precise therapeutic molecules for treatment are identified. The search for new drugs and repurposing of existing drugs are being performed; however, at the same time, research on plants to identify novel therapeutic compounds or testing the existing ones is progressing at a slower phase. In this context, genomics and biotechnology offer various tools and strategies to manipulate plants for producing those complex biopharmaceutical products. This review enumerates the scope for research on plant-based molecules for their potential application in treating SARS-CoV-2 infection. Strategies to edit gene and genome, overexpression and silencing approaches, and molecular breeding for producing target biomolecules in the plant system are discussed in detail. Altogether, the present review provides a roadmap for expediting research on using plants as a novel source of active biomolecules having therapeutic applications.