Development of SARS-CoV-2 Vaccine: Challenges and Prospects.

The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2.

Development of Computational In Silico Model for Nano Lipid Carrier Formulation of Curcumin.

The oral delivery system is very important and plays a significant role in increasing the solubility of drugs, which eventually will increase their absorption by the digestive system and enhance the drug bioactivity. This study was conducted to synthesize a novel curcumin nano lipid carrier (NLC) and use it as a drug carrier with the help of computational molecular docking to investigate its solubility in different solid and liquid lipids to choose the optimum lipids candidate for the NLCs formulation and avoid the ordinary methods that consume more time, materials, cost, and efforts during laboratory experiments. The antiviral activity of the formed curcumin-NLC against SARS-CoV-2 (COVID-19) was assessed through a molecular docking study of curcumin's affinity towards the host cell receptors. The novel curcumin drug carrier was synthesized as NLC using a hot and high-pressure homogenization method. Twenty different compositions of the drug carrier (curcumin nano lipid) were synthesized and characterized using different physicochemical techniques such as UV-Vis, FTIR, DSC, XRD, particle size, the zeta potential, and AFM. The in vitro and ex vivo studies were also conducted to test the solubility and the permeability of the 20 curcumin-NLC formulations. The NLC as a drug carrier shows an enormous enhancement in the solubility and permeability of the drug.

Plant as an Alternative Source of Antifungals against Aspergillus Infections: A Review.

Aspergillus species consists of a group of opportunistic fungi that is virulent when the immunity of the host is compromised. Among the various species, Aspergillus fumigatus is the most prevalent species. However, the prevalence of fungal infections caused by non-fumigatus Aspergillus has been increasing. Polyenes, echinocandins and azoles are the three main classes of antifungal agents being used for the treatment of aspergillosis. Nevertheless, the incidence of resistance towards these three classes has been rising over the years among several Aspergillus spp. The side effects associated with these conventional antifungal agents have also limited their usage. This urges the need for the discovery of a safe and effective antifungal agent, which presents a major challenge in medicine today. Plants present a rich source of bioactive molecules which have been proven effective against a wide range of infections and conditions. Therefore, this present review intends to examine the current literature available regarding the efficacy and mechanism of action of plant extracts and their compounds against Aspergillus spp. In addition, novel drug delivery systems of plant extracts against Aspergillus spp. were also included in this review.

Natural products from medicinal plants in Asia and the Pacific for RNA viruses: Hercules' fifth labour.

CONTEXT: The emergence of zoonotic viruses in the last decades culminating with COVID-19 and challenges posed by the resistance of RNA viruses to antiviral drugs requires the development of new antiviral drugs. OBJECTIVE: This review identifies natural products isolated from Asian and Pacific medicinal plants with in vitro and in vivo antiviral activity towards RNA viruses and analyses their distribution, molecular weights, solubility and modes of action. MATERIALS AND METHODS: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem and library search from 1961 to 2022. RESULTS: Out of about 350 molecules identified, 43 phenolics, 31 alkaloids, and 28 terpenes were very strongly active against at least one type of RNA virus. These natural products are mainly planar and amphiphilic, with a molecular mass between 200 and 400 g/mol and target viral genome replication. Hydroxytyrosol, silvestrol, lycorine, tylophorine and 12-O-tetradecanoylphorbol 13-acetate with IC50 below 0.01 µg/mL and selectivity index (S.I.) above 100 have the potential to be used for the development of anti-RNA virus leads. DISCUSSION AND CONCLUSIONS: The medicinal plants of Asia and the Pacific are a rich source of natural products with the potential to be developed as lead for the treatment of RNA viral infections.

Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle.

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of -8.1, -7.6, -7.0, and -7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.

COVID-19 Outcomes in Patients Hospitalised with Acute Myocardial Infarction (AMI): A Protocol for Systematic Review and Meta-Analysis

Background: Patients with cardiovascular disease and risk factors for cardiovascular illness are more likely to acquire severe 2019 novel coronavirus (2019-nCoV) infection (COVID-19). COVID-19 infection is more common in patients with cardiovascular illness, and they are more likely to develop severe symptoms. Nevertheless, whether COVID-19 patients are more likely to develop cardiovascular disorders such as acute myocardial infarction (AMI) is still up for debate. Methods: We will follow the preferred reporting items for systematic review and meta-analysis (PRISMA) to report our final study, including a systematic search of the bibliographic database using the appropriate combination of search terms or keywords. The choice of search terms is discussed in more detail later in this paper. The obtained results will be screened, and the data extracted from the studies selected for systematic review will be based on the predefined inclusion and exclusion criteria. Using the obtained data, we will then perform the associated Meta-analysis to generate the forest plot (pooled estimated effect size Hazard Ratio (HR) and 95% Confidence Intervals (CI) values) using the random-effects model. Any publication bias will be assessed using the funnel plot symmetry, Orwin and Classic Fail-Safe N Test and Begg and Mazumdar Rank Correlation Test and Egger’s Test of the intercept. In cases where insufficient data occur, we will also perform a qualitative review. Discussion: This systematic review will explore COVID-19 clinical outcomes, especially survival in patients hospitalised with Acute Myocardial Infarction, by utilising a collection of previously published data on hospitalised COVID-19 patients and Myocardial Infarction. Highlighting these prognostic survival analyses of COVID-19 patients with AMIT will have significant clinical implications by allowing for better overall treatment strategies and patient survival estimates by offering clinicians a method of quantitatively analysing the pattern of COVID-19 cardiac complications.