We describe updated information on the various vaccines available over the last two decades, along with recent progress in developing 63 diverse vaccines against SARS-CoV-2.

An amphiphilic phytochemical fraction isolated from methanol extract of Gymnema sylvestre leaf powder contained six terpenoids, two flavonoids, and one alkaloid that induced rapid flip-flop of fluorescent phospholipid analog in the phosphatidyl choline bilayer. Lipid-flipping activity of the methanol-extracted fraction of G. sylvestre (MEFGS) was dose-dependent and time-dependent with a rate constant k = (12.09 ± 0.94) mg –1 min –1 that was saturable at (40 ± 1) % flipping of the fluorescent lipid analogue. Interactions of MEFGS phytochemicals with large unilamelar vesicles led to time-dependent change in their rounded morphology into irregular shapes, indicating their membrane-destabilizing activity. MEFGS exhibited antibacterial activity on Escherichia coli (MTCC-118), Staphylococcus aureus (MTCC-212), and Pseudomonas aeruginosa (MTCC-1035) with IC 50 values 0.5, 0.35, and 0.1 mg/mL, respectively. Phytochemicals in MEFGS increased membrane permeabilization in all three bacteria, as indicated by 23, 17, and 17% increase in the uptake of crystal violet, respectively. MEFGS enhanced membrane damage, resulting in a 3–5 fold increase in leakage of cytosolic ions, 0.5–2 fold increase in leakage of PO 4 – , and 15–20% increase in loss of cellular proteins. MEFGS synergistically increased the efficacy of curcumin, amoxillin, ampicillin, and cefotaxime on S. aureus probably by enhancing their permeability into the bacterium. For the first time, our study reveals that phytochemicals from G. sylvestre enhance the permeability of the bacterial plasma membrane by facilitating flip-flop of membrane lipids. Lipid-flipping phytochemicals from G. sylvestre can be used as adjuvant therapeutics to enhance the efficacy of antibacterials by increasing their bioavailability in the target bacteria.

Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1 H, 13 C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma

A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carriers, nanoemulsions, nanogels, metal based nanoparticles, alike the future nanosystems through nanobubbles, nanofibers, nanodiamonds, nanotraps, nanorobots and eventually, the therapeutic applications of micro- and nanoparticulates, current status for clinical development against COVID-19 together with environmental implications of antivirals, gene therapy etc., which may be useful for repurposing and designing of novel antiviral drugs against various dreadful diseases, especially the SARS-CoV-2 and other associated variants.

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.