The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta coronavirus that belongs to the Coronaviridae family. Many clinically significant variants have emerged, as the virus's genome is prone to various mutations, leading to antigenic drift and resulting in evasion of host immune recognition. The current variants of concern (VOCs) include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), and P.1 (Gamma). The emerging variants contain various important mutations on the spike protein, leading to deleterious consequences, such as immune invasion and vaccine escape. These adverse effects result in increased transmissibility, morbidity, and mortality and the evasion of detection by existing or currently available diagnostic tests, potentially delaying diagnosis and treatment. This review discusses the key mutations present in the VOC strains and provides insights into how these mutations allow for greater transmissibility and immune evasion than the progenitor strain. Continuous monitoring and surveillance of VOC strains play a vital role in preventing and controlling the virus's spread.

Emerging SARS-CoV-2 Variants of Concern (VOCs): An Impending Global Crisis.

One year since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China, several variants of concern (VOC) have appeared around the world, with some variants seeming to pose a greater thread to public health due to enhanced transmissibility or infectivity. This study provides a framework for molecular characterization of novel VOC and investigates the effect of mutations on the binding affinity of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) using in silico approach. Notable nonsynonymous mutations in RBD of VOC include the E484K and K417N/T that can be seen in South African and Brazilian variants, and N501Y and D614G that can be seen in all VOC. Phylogenetic analyses demonstrated that although the UK-VOC and the BR-VOC fell in the clade GR, they have different mutation signatures, implying an independent evolutionary pathway. The same is true about SA-VOC and COH-VOC felling in clade GH, but different mutation signatures. Combining molecular interaction modeling and the free energy of binding (FEB) calculations for VOC, it can be assumed that the mutation N501Y has the highest binding affinity in RBD for all VOC, followed by E484K (only for BR-VOC), which favors the formation of a stable complex. However, mutations at the residue K417N/T are shown to reduce the binding affinity. Once vaccination has started, there will be selective pressure that would be in favor of the emergence of novel variants capable of escaping the immune system. Therefore, genomic surveillance should be enhanced to find and monitor new emerging SARS-CoV-2 variants before they become a public health concern.

https://www.mdpi.com/2076-2607/9/5/926/pdf

Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern

Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug-S protein binding and its potential therapeutic effect.

Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation.

/pdf/evaluating-the-in-vitro-efficacy-of-bovine-lactoferrin-1yck959o.pdf

Evaluating the in vitro efficacy of bovine lactoferrin products against SARS-CoV-2 variants of concern

BACKGROUND & OBJECTIVES Crimean-Congo hemorrhagic fever (CCHF) is a fatal disease, caused by a tick-borne virus (Nairovirus), having a high mortality rate. The study was aimed to evaluate the risk factors, the presenting symptoms and findings of the patients with prediagnosis of CCHF disease, and to compare these variables between the CCHF-positive and CCHF-negative patients. It was also aimed to develop a scoring formula for the diagnosis of CCHF. METHODS In total, 281 patients who were admitted to the Sabuncuoglu Serafeddin Training and Research Hospital, Amasya, Turkey between 2011 and 2015 and were prediagnosed with CCHF based on the clinical symptoms, laboratory findings and risk factors were included in the study. The definitive laboratory diagnosis of patients with prediagnosis of CCHF was ensured via molecular and serological methods. In addition, a mathematical diagnostic scoring formula was developed for enhancing the laboratory results of CCHF. RESULTS The ratio of certain clinical symptoms such as fever (p<0.001), headache (p<0.001), widespread body pain (p<0.001), fatigue (p = 0.001), nausea and vomiting (p = 0.013) in CCHF-positive patients were found to be significantly higher compared to the ratio in CCHF-negative patients. In terms of laboratory findings such as presence of leucopenia (p<0.001), creatine kinase (CK) elevation (p<0.001), thrombocytopenia (p<0.001), aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation (p<0.001), lactate dehydrogenase (LDH) levels (p = 0.002), absence of abnormal findings on chest radiograph (p = 0.042), and the absence of anaemia (p = 0.007), the CCHF-positive patients had higher rates in comparison to CCHF-negative ones. INTERPRETATION & CONCLUSION It was inferred that certain clinical symptoms and laboratory findings such as fever, headache, widespread body pain, fatigue, leucopenia, nausea, vomiting, high CK levels, thrombocytopenia, AST/ ALT elevation and elevated LDH levels are highly specific and are required to be considered in the definitive diagnosis of CCHF, particularly in regions where this infection is observed as endemic.

Examination of the specific clinical symptoms and laboratory findings of Crimean-Congo hemorrhagic fever.

Identifying mosquito species is a fundamental step in risk assessment and implementation of preventative strategies. Moreover, Culex pipiens is the most widespread mosquito vector in several regions of Iran and is the main vector for transmission of West Nile virus (WNV). Mosquitoes were collected at 14 sites in northern regions of Iran in 2015 and 2016. A subset of mosquito specimens was selected for identification confirmation using a DNA-barcoding technique. Construction of a phylogenetic tree showed clustering of mosquito sequences into three main genera: Aedes, Anopheles and Culex with individuals of a single species clustered closely together, regardless of where and when they were collected. Cx. pipiens complex and Cx. torrentium were identified and differentiated using multiplex real-time PCR targeting the gene locus for acetylcholinesterase 2 (ace2) to discriminate between Cx. pipiens pipiens and Cx. torrentium. The CQ11 microsatellite locus was used for discrimination between Cpp. biotypes. The predominant mosquito species in investigated regions were Cx. pipiens pipiens biotype pipiens, but we also detected Culex pipiens pipiens biotype molestus and hybrids of the two pipiens biotypes, as well as Cx. torrentium. The results of this study represent the first certain evidence of the presence of Cx. pipiens pipiens biotype molestus and hybrids between pipiens and molestus forms, and Cx. torrentium in Iran through a molecular identification approach. This report of a potentially important bridge vector for WNV might have key influence in the risk projections for WNV in Iran.

/pdf/dna-barcodes-corroborating-identification-of-mosquito-1ydad0y174.pdf

DNA barcodes corroborating identification of mosquito species and multiplex real-time PCR differentiating Culex pipiens complex and Culex torrentium in Iran.

SARS-CoV-2 spillover transmission due to recombination event

Morphological and molecular identification of Culicidae mosquitoes (Diptera: Culicidae) in Lorestan province, Western Iran.

Given current and projected changes in the climate, the composition of mosquito species is predicted to shift geographically with implications for the transmission dynamics of vector-borne pathogens. Many mosquito species are rarely collected in Canada and their history is poorly understood; thus assessing their potential role as vectors for pathogenesis is difficult. Mosquitoes were collected from four trapping sites in Quebec Province, Canada, from June to September during 2018 and 2019 using BG sentinel traps. From all morphologically identified female mosquitoes, at least one specimen was selected for identification confirmation using the DNA-barcoding technique. Sequences were subjected to alignment and a Neighbor-Joining (NJ) tree was created using Geneious software. In total, 2,752 female mosquitoes belonging to 20 species over five genera: including Aedes (Ae.), Anopheles (An.), Culex (Cx.), Culiseta (Cu.), Coquillettidia (Cq.) were collected. The predominant mosquito was found to be Ae. cinereus. The highest number of mosquito species was captured in July, followed by August, September, and then June. Five genera were characterized by a distinctive set of cytochrome oxidase I (COI) sequences that formed well-supported clusters in the NJ-tree. The presence of Ae.japonicus in Quebec provides an initial look at the distribution of mosquito species in eastern Canada, which may put Canadians at risk of a wider range of arboviruses.

Nariman Shahhosseini

Papers

Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern

DNA barcodes corroborating identification of mosquito species and multiplex real-time PCR differentiating Culex pipiens complex and Culex torrentium in Iran.

SARS-CoV-2 spillover transmission due to recombination event

Morphological and molecular identification of Culicidae mosquitoes (Diptera: Culicidae) in Lorestan province, Western Iran.

Mosquito Species Composition and Abundance in Quebec, Eastern Canada