Targeting the vital non-structural proteins (NSP12, NSP7, NSP8 and NSP3) from SARS-CoV-2 and inhibition of RNA polymerase by natural bioactive compound naringenin as a promising drug candidate against COVID-19.

The prevalence of SARS-CoV-2-induced respiratory infections is now a major challenge worldwide. There is currently no specific antiviral drug to prevent or treat this disease. Infection with COVID-19 seriously needs to find effective therapeutic agents. In the present study, naringenin, as a potential inhibitor candidate for RNA Polymerase SARS-CoV-2 was compared with remdesivir (FDA-approved drug) and GS-441,524 (Derivative of the drug remdesivir) by screening with wild-type and mutant SARS-CoV-2 NSP12 (NSP7-NSP8) and NSP3 interfaces, then complexes were simulated by molecular dynamics (MD) simulations to gain their stabilities. The docking results displayed ​scores of -3.45 kcal/mol and -4.32 kcal/mol against NSP12 and NSP3, respectively. Our results showed that naringenin had ΔG values more negative than the ΔG values of Remdesivir (RDV) and GS-441,524. Hence, naringenin was considered to be a potential inhibitor. Also, the number of hydrogen bonds of naringenin with NSP3 and later NSP12 are more than Remdesivir and its derivative. In this research, Mean root mean square deviation (RMSD) values of NSP3 and NSP12with naringenin ligand (5.55±1.58 nm to 3.45±0.56 nm and 0.238±0.01 to 0.242±0.021 nm, respectively showed stability in the presence of ligand. The root mean square fluctuations (RMSF) values of NSP3 and NSP12 amino acid units in the presence of naringenin in were 1.5 ± 0.31 nm and 0.118±0.058, respectively. Pharmacokinetic properties and prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of naringenin and RDV showed that ​these two compounds had no potential cytotoxicity.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses.

Cytokines produced by T helper cells (Th cells) have essential roles in the body's defense against viruses. Type 1 T helper (Th1) cells are essential for the host defense toward intracellular pathogens while T helper type 2 (Th2) cells are considered to be critical for the helminthic parasites' elimination swine-origin influenza A (H1N1) virus, a disease led to an epidemic in 2009 and rapidly spread globally via human-to-human transmission. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in 2020 and is a serious threat to the public health. Pulmonary immunopathology is the leading cause of death during influenza and SARS-CoV-2 epidemics and pandemics. Influenza and SARS-CoV-2 cause high levels of cytokines in the lung. Both inadequate levels and high levels of specific cytokines can have side effects. In this literature review article, we want to compare the Th1 and Th2 cells responses in SARS-CoV-2 and H1N1.