PheroxyPyrabenz and Carbopyrropyridin against major proteins of SARS CoV-2: a comprehensive in-silico molecular docking and dynamics simulation studies.

The pandemic that started in 2020 left us with so much information about viruses and respiratory diseases, and the cause behind it was severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The world is still recovering, which costs so many economic and other indirect disasters; despite that, no medications are available on the market. Although the WHO approved a few vaccines on an emergency basis, the remarks and the reinfection chances are still under investigation, and a few pharmaceutical companies are also claiming that a few medications can be effective. However, there is no situation in control. SARS CoV-2 mutates and comes in different forms, making the situation unpredictable. In this study, we have screened the complete Asinex's BioDesign library, which contains 170,269 compounds, and shorted the data against the docking score that helps in the identification of 4-[5-(3-Ethoxy-4-hydroxyphenyl)-1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1, 2-benzenediol (PheroxyPyrabenz) and 1-[(3R,4R)-1-(5-Aminopentanoyl)-4-hydroxy-3-pyrrolidinyl]-1H-pyrrolo[2,3-b]pyridine-4-carboxamide (Carbopyrropyridin) as a significant drug candidate that can work against the multiple proteins of the SARS CoV-2 resulting in seizing the complete biological process of the virus. Further, the study extended to Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and molecular dynamics (MD) simulation of both the compounds with their complexity. The complete workflow of the study has shown satisfactory results, and both drug candidates can potentially stop the hunt for drugs against this virus after its experimental validation. Further, we checked both compounds' absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, showing case-proof validatory results.Communicated by Ramaswamy H. Sarma.

In Vitro Evaluation of Leuconostoc mesenteroides Cell-Free-Supernatant GBUT-21 against SARS-CoV-2.

The unprecedented health catastrophe derived from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 infection) met with a phenomenal scientific response across the globe. Worldwide, the scientific community was focused on finding a cure for the deadly disease. A wide range of research studies has consistently revealed the link between SARS-CoV-2 infection severity and abnormal gut microbiomes, suggesting its potential in developing novel therapeutic approaches. Probiotics have been extensively studied to promote health in human hosts and reestablish a balance in the dysbiotic gut microbiome; however, there is strong skepticism about their safety and efficacy. Consequently, the metabolic signatures of probiotics, often referred to as "postbiotics", could prove of paramount importance for adjuvant cures in patients with SARS-CoV-2. Postbiotics exhibit safety, enhanced shelf-life, and stability and, therefore, could be implemented in SARS-CoV-2 prophylactic strategies with no undue adverse side effects. The current study is a preliminary investigation of the antiviral properties of postbiotic metabolites derived from Leuconostoc mesenteroides GBUT-21. The study focuses on the potential biological role in inactivating SARS-CoV-2 and reducing related inflammatory pathways.

Clinical and Serological Findings of COVID-19 Participants in the Region of Makkah, Saudi Arabia.

Makkah in Saudi Arabia hosts the largest annual religious event in the world. Despite the many strict rules enacted, including Hajj cancellation, city lockdowns, and social distancing, the region has the second highest number of new COVID-19 cases in Saudi Arabia. Public health interventions that identify, isolate, and manage new cases could slow the infection rate. While RT-PCR is the current gold standard in SARS-CoV-2 identification, it yields false positive and negative results, which mandates the use of complementary serological tests. Here, we report the utility of serological assays during the acute phase of individuals with moderate and severe clinical manifestations of SARS-CoV-2 (COVID19). Fifty participants with positive RT-PCR results for SARS-CoV-2 were enrolled in this study. Following RT-PCR diagnosis, serum samples from the same participants were analyzed using in-house ELISA (IgM, IgA, and IgG) and microneutralization test (MNT) for the presence of antibodies. Of the 50 individuals analyzed, 43 (86%) showed a neutralizing antibody titer of ≥20. Univariate analysis with neutralizing antibodies as a dependent variable and the degree of disease severity and underlying medical conditions as fixed factors revealed that patients with no previous history of non-communicable diseases and moderate clinical manifestation had the strongest neutralizing antibody response "Mean: 561.11". Participants with severe symptoms and other underlying disorders, including deceased individuals, demonstrated the lowest neutralizing antibody response. Anti-spike protein antibody responses, as measured by ELISA, showed a statistically significant correlation with neutralizing antibodies. This reinforces the speculation that serological assays complement molecular testing for diagnostics; however, patients' previous medical history (anamnesis) should be considered in interpreting serological results.

Exploring Toxins for Hunting SARS-CoV-2 Main Protease Inhibitors: Molecular Docking, Molecular Dynamics, Pharmacokinetic Properties, and Reactome Study.

The main protease (Mpro) is a potential druggable target in SARS-CoV-2 replication. Herein, an in silico study was conducted to mine for Mpro inhibitors from toxin sources. A toxin and toxin-target database (T3DB) was virtually screened for inhibitor activity towards the Mpro enzyme utilizing molecular docking calculations. Promising toxins were subsequently characterized using a combination of molecular dynamics (MD) simulations and molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. According to the MM-GBSA binding energies over 200 ns MD simulations, three toxins-namely philanthotoxin (T3D2489), azaspiracid (T3D2672), and taziprinone (T3D2378)-demonstrated higher binding affinities against SARS-CoV-2 Mpro than the co-crystalized inhibitor XF7 with MM-GBSA binding energies of -58.9, -55.9, -50.1, and -43.7 kcal/mol, respectively. The molecular network analyses showed that philanthotoxin provides a ligand lead using the STRING database, which includes the biochemical top 20 signaling genes CTSB, CTSL, and CTSK. Ultimately, pathway enrichment analysis (PEA) and Reactome mining results revealed that philanthotoxin could prevent severe lung injury in COVID-19 patients through the remodeling of interleukins (IL-4 and IL-13) and the matrix metalloproteinases (MMPs). These findings have identified that philanthotoxin-a venom of the Egyptian solitary wasp-holds promise as a potential Mpro inhibitor and warrants further in vitro/in vivo validation.