Biocomputational characterisation of MBO_200107 protein of Mycobacterium tuberculosis variant caprae: a molecular docking and simulation study.

The principal objective of this study was to delineate the potentiality of the MBO_200107 protein from the Mycobacterium tuberculosis variant caprae in cancer research. It is a cytoplasmic protein, comprised of a 354-long amino acid chain, alkaline, had a molecular weight of 39089.37 Da, an isoelectric point of 9.62 and a grand average of hydropathicity of -0.345. One of the functional domains was predicted as Gammaglutamylcyclotransferase (GGCT). Among tertiary structures, the Modeller and Phyre2 model satisfied all the quality parameters, though they are truncated; contrarily, the I-TASSER model is full length and contains the sequence for the GGCT domain, though it did not meet all the quality parameters. It also has significant sequence similarities (47.5% by EMBOSS Water and 72.4% by EMBOSS Matcher) with a human GGCT, and the conserved sequences are confined to the GGCT domain of the MBO_200107. According to molecular docking analyses, the protein has a binding affinity of -4.8 kcal/mol by Autodock Vina and -56.465 kcal/mol by HPEPDOCK to the human glutathione (GSH), an essential metabolite for GGCT metabolism. The Molecular dynamic simulation of the docked complex showed the binding efficiency of the GSH to MBO_200107 with a minimal structural alteration. The in silico findings mentioned above revealed that the protein could be used as a supplementary tool in cancer research, such as designing vaccines or drugs where the role of GGCT has been implicated. Further, we recommend fully characterising the protein and conducting essential in vitro and in vivo experiments to determine its detailed usefulness.Communicated by Ramaswamy H. Sarma.

Coinfection of fungi with SARS-CoV-2 is a detrimental health risk for COVID-19 patients.

Background: Notable fungal coinfections with SARS-CoV-2 in COVID-19 patients have been reported worldwide in an alarming way. Mucor spp. and Rhizopus spp. were commonly known as black fungi, whereas Aspergillus spp. and Candida spp. were designated as white fungi implicated in those infections. In this review, we focused on the global outbreaks of fungal coinfection with SARS-CoV-2, the role of the human immune system, and a detailed understanding of those fungi to delineate the contribution of such coinfections in deteriorating the health conditions of COVID-19 patients based on current knowledge. Main body: Impaired CD4 + T cell response due to SARS-CoV-2 infection creates an opportunity for fungi to take over the host cells and, consequently, cause severe fungal coinfections, including candidiasis and candidemia, mucormycosis, invasive pulmonary aspergillosis (IPA), and COVID-19-associated pulmonary aspergillosis (CAPA). Among them, mucormycosis and CAPA have been reported with a mortality rate of 66% in India and 60% in Colombia. Moreover, IPA has been reported in Belgium, Netherlands, France, and Germany with a morbidity rate of 20.6%, 19.6%, 33.3%, and 26%, respectively. Several antifungal drugs have been applied to combat fungal coinfection in COVID-19 patients, including Voriconazole, Isavuconazole, and Echinocandins. Conclusion: SARS-CoV-2 deteriorates the immune system so that several fungi could take that opportunity and cause life-threatening health situations. To reduce the mortality and morbidity of fungal coinfections, it needs immunity boosting, proper hygiene and sanitation, and appropriate medication based on the diagnosis.

A comprehensive review on COVID-19 vaccines: development, effectiveness, adverse effects, distribution and challenges.

The present SARS-CoV-2 induced COVID-19 pandemic is responsible for millions of deaths, illnesses, and economic loss worldwide. There are 21 COVID-19 vaccines from different platforms approved worldwide for emergency use until 13 August 2021. Later, BNT162b2 obtained full approval from the FDA. The efficacy of the leading vaccines such as BNT162b2, mRNA-1273, Gam-Covid-Vac, Ad26.COV2.S, ChAdOx1 nCoV-19, and BBIBP-CorV, against SARS-CoV-2 documented as 95%, 94.1%, 91.6%, 67%, 70.4%, and 78.1%, respectively. Moreover, against the Delta variant of SARS-CoV-2, BNT162b2, ChAdOx1 nCoV-19, and BBV152 showed 88%, 70%, and 65.2% efficacy, respectively. Apart from the common adverse effects such as fever, fatigue, headache, and pain in the injection site, Bell's palsy with BNT162b2, myocarditis and pericarditis with mRNA-1273, and thrombosis with ChAdOx1 nCoV-19 have been reported though seemed not alarming. Furthermore, global production and distribution of vaccines should be ensured in an equal and justifiable way that the immunity and protection against the virus would be optimum and persistent.

Computational Designing and Prediction of ADMET Properties of Four Novel Imidazole-based Drug Candidates Inhibiting Heme Oxygenase-1 Causing Cancers.

The overexpression of heme oxygenase-1 (HO-1) contributes to the development of several types of cancers. The inhibition of HO-1 through imidazole-based drugs, which is non-competitive with heme, is a focus of anticancer drug research. We designed the four following novel HO-1 inhibiting compounds: 2-(1-cyclopentyl-4-(1H-imidazol-4-yl)butan-2-yl)pyrazine (M11), 2-[(2-chloro-3-methylcyclohexyl)methyl]-1H-imidazole (M26), 2-(2-phenethyl-1H-imidazol-4-yl)ethanesulfonamide (M28), and 5-chloro-2-[2-(2,5-dihydro-1H-imidazol-2-yl)propan-2-yl]-1H-imidazole (M31). All compounds showed a strong binding affinity with HO-1 in molecular docking studies. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) data showed that the compounds would be available orally in an acceptable manner. The bioactivity scores revealed that they were moderately active substances. They were found as non-mutagen, non-tumorigenic, non-irritant, and non-detrimental to the reproductive system. Finally, the drug-likeness values of the compounds were obtained as -0.71, -1.64, -2.04, and 0.4 respectively, with the final drug-score of 0.60, 0.54, 0.51, and 0.77 respectively.

Coronaviruses in wild birds - A potential and suitable vector for global distribution.

The recurrent appearance of novel coronaviruses (CoVs) and the mortality and morbidity caused by their outbreaks aroused a widespread response among the global science community. Wild birds' high biodiversity, perching and migratory activity, ability to travel long distances and possession of a special adaptive immune system may make them alarming sources of zoonotic CoV-spreading vectors. This review gathers the available evidence on the global spread of CoVs in wild birds to date. The major wild birds associated with different types of CoVs are Anseriformes, Charadriiformes, Columbiformes, Pelecaniformes, Galliformes, Passeriformes, Psittaciformes, Accipitriformes, Ciconiiformes, Gruiformes and so on. However, the main type of CoVs found in wild birds is gammacoronavirus, followed by deltacoronavirus. Consequently, it is imperative to enable thorough research and continuous monitoring to fill the study gap in terms of understanding their role as zoonotic vectors and the frequent appearance of novel CoVs.