COVID-19 Therapeutic Potential of Natural Products.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines.

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization's Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations.

Chitosan and its derivatives as polymeric anti-viral therapeutics and potential anti-SARS-CoV-2 nanomedicine.

The coronavirus pandemic, COVID-19 has a global impact on the lives and livelihoods of people. It is characterized by a widespread infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where infected patients may develop serious medical complications or even face death. Development of therapeutic is essential to reduce the morbidity and mortality of infected patients. Chitosan is a versatile biomaterial in nanomedicine and exhibits anti-microbial, anti-cancer and immunomodulatory properties. This review highlights the progress in chitosan design and application pertaining to the anti-viral effects of chitosan and chitosan derivatives (hydroxypropyl trimethylammonium, sulfate, carboxymethyl, bromine, sialylglycopolymer, peptide and phosphonium conjugates) as a function of molecular weight, degree of deacetylation, type of substituents and their degree and site of substitution. The physicochemical attributes of these polymeric therapeutics are identified against the possibility of processing them into nanomedicine which can confer a higher level of anti-viral efficacy. The designs of chitosan for the purpose of targeting SARS-CoV-2, as well as the ever-evolving strains of viruses with a broad spectrum anti-viral activity to meet pandemic preparedness at the early stages of outbreak are discussed.

The effectiveness of various gargle formulations and salt water against SARS-CoV-2.

The COVID-19 is difficult to contain due to its high transmissibility rate and a long incubation period of 5 to 14 days. Moreover, more than half of the infected patients were young and asymptomatic. Virus transmission through asymptomatic patients is a major challenge to disease containment. Due to limited treatment options, preventive measures play major role in controlling the disease spread. Gargling with antiseptic formulation may have potential role in eliminating the virus in the throat. Four commercially available mouthwash/gargle formulations were tested for virucidal activity against SARS-CoV-2 in both clean (0.3 g/l BSA) and dirty (0.3 g/l BSA + 3 mL/L human erythrocytes) conditions at time points 30 and 60 s. The virus was isolated and propagated in Vero E6 cells. The cytotoxicity of the products to the Vero E6 was evaluated by kill time assay based on the European Standard EN14476:2013/FprA1:2015 protocol. Virus titres were calculated as 50% tissue culture infectious dose (TCID50/mL) using the Spearman-Karber method. A reduction in virus titer of 4 log10 corresponds to an inactivation of ≥ 99.99%. Formulations with cetylperidinium chloride, chlorhexidine and hexitidine achieved > 4 log10 reduction in viral titres when exposed within 30 s under both clean and dirty conditions. Thymol formulations achieved only 0.5 log10 reduction in viral titres. In addition, salt water was not proven effective. Gargle formulations with cetylperidinium chloride, chlorhexidine and hexetidine have great potential in reducing SAR-CoV-2 at the source of entry into the body, thus minimizing risk of transmission of COVID-19.

Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase.

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.

In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice.

Introduction Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by a number of national COVID-19 guidance documents for dental settings.Aim To assess the in vitrovirucidal activity of an oral povidone iodine (PVP-I) product against SARS-CoV-2.Material and methods BETADINE gargle and mouthwash (1% PVP-I) was tested against SARS-CoV-2 virus under both clean and dirty conditions using a suspension assay based on EN14476 methodology. Virucidal activity of the product, undiluted and at 1:2 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50/ml).Results The undiluted product achieved >5 log10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in both clean and dirty conditions.Conclusion PVP-I gargle and mouthwash product, undiluted and at 1:2 dilution, demonstrated potent and rapid virucidal activity (≥4 log10 reduction of viral titre) in 15 seconds against SARS-CoV-2 in vitro. The PVP-I gargle and mouthwash product is widely available and could be readily integrated into infection control measures during dental treatment including pre-procedural oral decontamination.