The coronavirus pandemic caused by the SARS-CoV-2 virus, which humanity resisted using the latest advances in science, left behind, among other things, extensive genetic data. Every day since the end of 2019, samples of the virus genomes have been collected around the world, which makes it possible to trace its evolution in detail from its emergence to the present. The accumulated statistics of testing results showed that the number of confirmed cases of SARS-CoV-2 infection was at least 767.5 million (9.5 % of the current world population, excluding asymptomatic people), and the number of sequenced virus genomes is more than 15.7 million (which is over 2 % of the total number of infected people). These new data potentially contain information about the mechanisms of the variability and spread of the virus, its interaction with the human immune system, the main parameters characterizing the mechanisms of the development of a pandemic, and much more. In this article, we analyze the space of possible variants of SARS-CoV-2 genetic sequences both from a mathematical point of view and taking into account the biological limitations inherent in this system, known both from general biological knowledge and from the consideration of the characteristics of this particular virus. We have developed software capable of loading and analyzing SARS-CoV-2 nucleotide sequences in FASTA format, determining the 5’ and 3’ UTR positions, the number and location of unidentified nucleotides (“N”), performing alignment with the reference sequence by calling the program designed for this, determining mutations, deletions and insertions, as well as calculating various characteris tics of virus genomes with a given time step (days, weeks, months, etc.). The data obtained indicate that, despite the apparent mathematical diversity of possible options for changing the virus over time, the corridor of the evolutionary  trajectory that the coronavirus has passed through seems to be quite narrow. Thus it can be assumed that it is determined to some extent, which allows us to hope for a possibility of modeling the evolution of the coronavirus. 

On the space of SARS-CoV-2 genetic sequence variants

The comparison of the development of the SARS-CoV-2 epidemic in several neighboring regions can help researchers to assess the risks and develop more effective strategies and approaches in the field of preventive medicine. We analyzed the infection and mortality statistics for the 2020–2022 period in ten individual regions of the Siberian Federal District of Russia. We also sequenced complete genomes, which allowed us to analyze the genetic diversity of SARS-CoV-2 circulated in each of the ten regions and to build a phylogenetic dendrogram for the virus variants. The ParSeq v.1.0 software was developed to automate and speed up the processing and analysis of viral genomes. At the beginning of the pandemic, in the first two waves, the B.1.1 variant (20B) dominated in all regions of the Siberian Federal District. The third and fourth waves were caused by the Delta variant. Mortality during this period was at a maximum; the incidence was quite high, but the number of deposited genomes with GISAID during this period was extremely low. The maximum incidence was at the beginning of 2022, which corresponds to the arrival of the Omicron variant in the region. The BA.5.2 variant became the dominant one. In addition, by using NextClade, we identified three recombinants in the most densely populated areas.

The Development of the SARS-CoV-2 Epidemic in Different Regions of Siberia in the 2020–2022 Period

The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro , iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape. 

A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants

A previously unknown coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was isolated in Wuhan, China in December 2019, from a patient with a respiratory disease linked to potential contact with wild animals [...]. 

Editorial for SARS-CoV-2 and COVID-19 Topical Collection

The COVID-19 epidemic demanded the rapid development of high-affinity molecules of different types aimed at a single target, the S-protein of SARS-CoV-2. The simultaneous development and testing of such molecules provide a unique opportunity to compare the features of biotechnological platforms for creating therapeutic proteins. This review considers classical antibodies, variable lymphocyte receptors, single-domain antibodies, and artificial scaffolds (DARPins, affibodies, VH), that are compared in terms of affinity, neutralizing activity, size and compatibility with different delivery methods. It can be concluded that all platforms used have produced high-affinity proteins that specifically bind to the coronavirus S-protein. The highest affinity of the targeting molecules with the virus protein was achieved by developing classical antibodies, nanobodies and by combining several binding modules into multivalent constructs with high avidity. Based on the results of &lt;i&gt;in vivo&lt;/i&gt; experiments, it can be concluded that a high affinity of the therapeutic protein for the surface antigens of SARS-CoV-2 is a necessary but not sufficient condition for suppression of COVID-19 due to the peculiarities of the biology of this virus. The experience gained in the development of therapeutic agents against coronavirus will be useful for design of effective targeted drugs for the treatment of known and new viral infections.&lt;br&gt;The bibliography includes 126 references. 

Design of targeted antiviral polypeptides specific to SARS-CoV-2. Challenges and prospects

In this retrospective, single-center study, we conducted an analysis of 13,699 samples from different individuals obtained from the Federal Research Center of Fundamental and Translational Medicine, from 1 April to 30 May 2020 in Novosibirsk region (population 2.8 million people). We identified 6.49% positive for SARS-CoV-2 cases out of the total number of diagnostic tests, and 42% of them were from asymptomatic people. We also detected two asymptomatic people, who had no confirmed contact with patients with COVID-19. The highest percentage of positive samples was observed in the 80+ group (16.3%), while among the children and adults it did not exceed 8%. Among all the people tested, 2423 came from a total of 80 different destinations and only 27 of them were positive for SARS-CoV-2. Out of all the positive samples, 15 were taken for SARS-CoV-2 sequencing. According to the analysis of the genome sequences, the SARS-CoV-2 variants isolated in the Novosibirsk region at the beginning of the pandemic belonged to three phylogenetic lineages according to the Pangolin classification: B.1, B.1.1, and B.1.1.129. All Novosibirsk isolates contained the D614G substitution in the Spike protein, two isolates werecharacterized by an additional M153T mutation, and one isolate wascharacterized by the L5F mutation.

/pdf/genomic-and-epidemiological-features-of-covid-19-in-the-2oxd2ldl.pdf

Genomic and Epidemiological Features of COVID-19 in the Novosibirsk Region during the Beginning of the Pandemic

The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan’s RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1. We show that initial immunization induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection with the ancestral Wuhan virus. These nanobodies, however, mostly lacked the activity against SARS-CoV-2 omicron-pseudotyped viruses. In contrast, serial immunization with different RBD variants resulted in the generation of nanobodies demonstrating a higher degree of somatic mutagenesis and a broad range of neutralization. Four nanobodies recognizing distinct epitopes were shown to potently neutralize a spectrum of omicron variants, including those of the XBB sublineage. Our data show that nanobodies broadly neutralizing SARS-CoV-2 variants may be readily induced by a serial variant RBD immunization.

Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies

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Genomic and Epidemiological Features of COVID-19 in the Novosibirsk Region during the Beginning of the Pandemic

Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies