Monkeypox: epidemiology, mode of transmission, clinical features, genetic clades and molecular properties.

OBJECTIVE: Recently monkeypox cases have been reported from many non-endemic countries. The objective of this article is to bring out the epidemiology, mode of transmission, clinical features, genetic clades, and molecular properties of monkeypox virus. MATERIALS AND METHODS: A detailed literature review was conducted on monkeypox, using databases PubMed/Medline, EMBASE, PMC and Cochrane Library, for the period between 1985 to 2022. RESULTS: Genetically monkeypox virus can be classified into Central African clade and Western African clades. The sequence similarity between the two strains was found to be 99.5%. However, some significant differences were found in the virulent and nonvirulent genes of the strains, such as BR-203, BR-209, COP-C3L b and COP-H5R, COP-A9L, COP-A50R, and COP-A36R, respectively. Human to human transmission occurs after exposure to respiratory droplets, oral secretions, contact with lesions, fomites, and direct/sexual contact. Monkeypox can also be transmitted from the infected mother to the fetus through the placenta leading to congenital infection. In May 2022 several cases have been reported from Europe, North America, and Australia, particularly from homosexual men. CONCLUSIONS: Monkeypox is a zoonotic disease which was prevalent in Central and Western African countries. Recently, human to human spread was noticed in developed countries of Europe, North America and Australia. Despite with a close genetic similarity between the two clades, the Central African strain is comparatively very virulent with high mortality. Monkeypox should be considered a re-emerging, neglected disease and proper measures like hand hygiene, wearing masks and vaccination to the high-risk groups are advised.

Short report - Lethal and aggressive pancreatic cancer: molecular pathogenesis, cellular heterogeneity, and biomarkers of pancreatic ductal adenocarcinoma.

This short report describes the carcinogenesis of the pancreas leading to pancreatic ductal adenocarcinoma (PDAC) determined by molecular, cellular, and functional heterogeneity. Among the diverse types of pancreatic cancers, PDAC is the most lethal, aggressive, and one of the leading cancers associated with the highest mortality. Pancreatic cellular components like pancreatic stellate cells (PSC), mesenchymal stem cells (MSC), and pancreatic fibroblast cells (PFC) exhibit these properties in PDAC. After the appearance of point mutations in KRAS, the mutations in tumor suppressor genes appear sequentially in the order of CDKN2A, TP53, and SMAD4 that eventually resulting in PDAC development. As of today, there are no effective therapeutic options or treatments available for PDAC. The main difficulty in managing PDAC cases is its defiance to chemotherapy and radiotherapy. There were several attempts to identify a suitable biomarker for the early diagnosis and prognosis of PDAC. Anyway, these recently discovered biomarkers vary in their sensitivity and specificities. Some of the other important and reliable biomarkers for PDAC are carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cell migration-inducing hyaluronan binding protein (CEMIP), serum fatty acid metabolite PC-594, and micro-RNAs (miRNAs).

Evolving biothreat of variant SARS-CoV-2 - molecular properties, virulence and epidemiology.

SARS-CoV-2 are enveloped RNA viruses that belong to the family Coronaviridae of genus Beta coronavirus, responsible for the COVID-19 pandemic. The mutation rate is high among RNA viruses and in particular, coronavirus replication is error prone with an estimated mutation rate of 4x10-4 nucleotide substitutions per site per year. Variants of SARS-CoV-2 have been reported from various countries like United Kingdom, South Africa, Denmark, Brazil and India. These variants evolved due to mutations in spike gene of SARS-CoV-2. The most concerning variants are Variant of Concern (VOC) 202012/01 from United Kingdom and B.1.617 variant of India. Other variants include B.1.351 lineages, cluster 5/SARS-CoV-2 variant of Denmark, 501.V2 variant/SARS-CoV-2 variant of South Africa, lineage B.1.1.248/lineage P.1 of Brazil. Mutations in S protein may result in changes in the transmissibility and virulence of SARS-CoV-2. To date, alterations in virulence or pathogenicity have been reported among the variants from many parts of the globe. In our opinion, since the S protein is significantly altered, the suitability of existing vaccine specifically targeting the S protein of SARS-CoV-2 variants is a major concern. The mutations in SARS-CoV-2 are a continuous and evolving process that may result in the transformation of naïve SARS-CoV-2 into totally new subsets of antigenically different SARS-CoV-2 viruses over a period of time.

Omicron (B.1.1.529) - variant of concern - molecular profile and epidemiology: a mini review.

Recently a new variant of SARS-CoV-2 was reported from South Africa. World Health Organization (WHO) named this mutant as a variant of concern - Omicron (B.1.1.529) on 26th November 2021. This variant exhibited more than thirty amino acid mutations in the spike protein. This mutation rate is exceeding the other variants by approximately 5-11 times in the receptor-binding motif of the spike protein. Omicron (B.1.1.529) variant might have enhanced transmissibility and immune evasion. This new variant can reinfect individuals previously infected with other SARS-CoV-2 variants. Scientists expressed their concern about the efficacy of already existing COVID-19 vaccines against Omicron (B.1.1.529) infections. Some of the crucial mutations that are detected in the receptor-binding domain of the Omicron variant have been shared by previously evolved SARS-CoV-2 variants. Based on the Omicron mutation profile in the receptor-binding domain and motif, it might have collectively enhanced or intermediary infectivity relative to its previous variants. Due to extensive mutations in the spike protein, the Omicron variant might evade the immunity in the vaccinated individuals.

COVID-19 (Novel Coronavirus 2019) - recent trends.

The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.

Structure of the RNA-binding domain of Nodamura virus protein B2, a suppressor of RNA interference.

Protein B2 from Nodamura virus (NMV B2), a member of the Nodavirus family, acts as a suppressor of RNA interference (RNAi). The N-terminal domain of NMV B2, consisting of residues 1-79, recognizes double-stranded RNA (dsRNA). The 2.5 A crystal structure of the RNA-binding domain of NMV B2 shows a dimeric, helical bundle structure. The structure shows a conserved set of RNA-binding residues compared with flock house virus B2, despite limited sequence identity. The crystal packing places the RNA-binding residues along one face of symmetry-related molecules, suggesting a potential platform for recognition of dsRNA.