The emerging global infectious COVID-19 coronavirus disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.
The ongoing global pandemic of infection disease COVID-19 caused by the 2019 novel coronavirus (SARS-COV-2, formerly 2019-nCoV) presents critical threats to public health and the economy since it was identified in China, December 2019. The genome of SARS-CoV-2 had been sequenced and structurally annotated, yet little is known of the intrinsic organization and evolution of the genome. To this end, we present a mathematical method for the genomic spectrum, a kind of barcode, of SARS-CoV-2 and common human coronaviruses. The genomic spectrum is constructed according to the periodic distributions …
Since the first reports of a coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome virus (SARS-CoV-2) in Wuhan, Hubei province, China, scientists are working around the clock to find sound answers to the issue of its origin. While the number of scientific articles on SARS-CoV-2 is increasing, there are still many gaps as to its origin. All studies failed to find a coronavirus in other animals that is more similar to human SARS-COV2 than the bat virus, considered to be the primary reservoir. In this paper we address a new hypothesis, based on a possible recombina…
Coronaviruses have recently caused world-wide severe outbreaks: SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle-East Respiratory Syndrome) in 2012. At the end of 2019, a new coronavirus outbreak appeared in Wuhan (China) seafood market as first focus of infection, becoming a pandemics in 2020, spreading mainly into Europe and Asia. Although the virus family is well-known, this specific virus presents considerable differences, as higher transmission rates, being a challenge for diagnostic methods, treatments and vaccines. Coronavirus(C++).pro is a C++ application which simulat…
SARS-CoV-2 is a new human coronavirus (CoV), which emerged in China in late 2019 and is responsible for the global COVID-19 pandemic that caused more than 59 million infections and 1.4 million deaths in 11 months. Understanding the origin of this virus is an important issue and it is necessary to determine the mechanisms of its dissemination in order to contain future epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available on the virus, we discuss the different scenarios evoked to…
Zhou et al. reported the discovery of RmYN02, a strain closely related to SARS-CoV-2, which is claimed to contain a natural PAA amino acid insertion at the S1/S2 junction of the spike protein at the same position of the PRRA insertion that has created a polybasic furin cleavage site in SARS-CoV-2. The authors support with their findings the theory that the furin cleavage site insertion present in SARS-CoV-2 is natural. Because no nucleotide alignment with closely related strains of the region coding for the supposed insertion is provided by Zhou et al., we have applied several alignment algori…
Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativen…
Metagenomic datasets from pangolin tissue specimens have previously yielded SARS-related coronaviruses which show high homology in their receptor binding domain to SARS-CoV-2, suggesting a potential zoonotic source for this feature of the human virus, possibly via recombination (Liu et al. 2019, Lam et al. 2020, Xiao et al. 2020, Liu et al. 2020). Here we re-examine these published datasets. We report that only a few pangolin samples were found to contain coronavirus reads, and even then in low abundance, while other non-pangolin hosted viruses were present in higher abundance. We also discove…
The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance to the controlling and combating of coronavirus disease 2019 (COVID-19) pandemic. Currently, near 15,000 SARS-CoV-2 single mutations have been recorded, having a great ramification to the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2 evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response…
Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-…
(1) Background: RNA viruses and especially coronaviruses could act inside host cells not only by building their own proteins, but also by perturbing the cell metabolism. We show the possibility of miRNA-like inhibitions by the SARS-CoV-2 concerning for example the hemoglobin and type I interferons syntheses, hence highly perturbing oxygen distribution in vital organs and immune response as described by clinicians; (2) Methods: We compare RNA subsequences of SARS-CoV-2 protein S and RNA-dependent RNA polymerase genes to mRNA sequences of beta-globin and type I interferons; (3) Results: RNA subs…
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations we…
Despite of the fast development of highly effective vaccines to control the current COVID$-$19 pandemic, the unequal distribution and availability of these vaccines worldwide and the number of people infected in the world lead to the continuous emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) variants of concern. It is likely that real-time genomic surveillance will be continuously needed as an unceasing monitoring tool, necessary to follow the spillover of the disease spread and the evolution of the virus. In this context, new genomic variants of SARS-CoV-2 that may e…
This paper presents an analysis of the publication of datasets collected via Google Dataset Search, specialized in families of RNA viruses, whose terminology was obtained from the National Cancer Institute (NCI) thesaurus developed by the US Department of Health and Human Services. The objective is to determine the scope and reuse capacity of the available data, determine the number of datasets and their free access, the proportion in reusable download formats, the main providers, their publication chronology, and to verify their scientific provenance. On the other hand, we also define possibl…
RaTG13 is the closest related coronavirus genome phylogenetically to SARS-CoV-2, consequently understanding its provenance is of key importance to understanding the origin of the COVID-19 pandemic. The RaTG13 NGS dataset is attributed to a fecal swab from the intermediate horseshoe bat Rhinolophus affinis. However, sequence analysis reveals that this is unlikely. Metagenomic analysis using Metaxa2 shows that only 10.3 % of small subunit (SSU) rRNA sequences in the dataset are bacterial, inconsistent with a fecal sample, which are typically dominated by bacterial sequences. In addition, the bac…
Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2500 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. Th…
A manuscript identified bat sarbecoviruses with high sequence homology to SARS-CoV-2 found in caves in Laos that can directly infect human cells via the human ACE2 receptor (Coronaviruses with a SARS-CoV-2-like receptor binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula, Temmam S., et al.). Here, I examine the genomic sequence of one of these viruses, BANAL-236, and show it has 5-UTR and 3-UTR secondary structures that are non-canonical and, in fact, have never been seen in an infective coronavirus. Specifically, the 5-UTR has a 177 nt copy…
Worldwide Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is disrupting in the economy and anxiety of people. The public anxiety has increased the psychological burden on government and healthcare professionals, resulting in a government worker suicide in Japan. The terrified people are asking the government for border measures. However, are border measures possible for this virus? By analyzing 48 almost complete virus genome sequences, we found out that the viruses that invaded Taiwan, the United States, and Japan were introduced independently. We identified thirteen pa…
The 2019 coronavirus disease (COVID-19) became a worldwide pandemic with currently no effective antiviral drug except treatments for symptomatic therapy. Flux balance analysis is an efficient method to analyze metabolic networks. It allows optimizing for a metabolic function and thus e.g., predicting the growth rate of a specific cell or the production rate of a metabolite of interest. Here flux balance analysis was applied on human lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reposition metabolic drugs and drug combinations against the replication o…
There is a near consensus view that SARS-CoV-2 has a natural zoonotic origin; however, several characteristics of SARS-CoV-2 taken together are not easily explained by a natural zoonotic origin hypothesis. These include: a low rate of evolution in the early phase of transmission; the lack of evidence of recombination events; a high pre-existing binding to human ACE2; a novel furin cleavage site insert; a flat glycan binding domain of the spike protein which conflicts with host evasion survival patterns exhibited by other coronaviruses, and high human and mouse peptide mimicry. Initial assumpti…
The phylogenetic tree of SARS-CoV-2 (nCov-19) viruses is reconstructed according to the similarity of genome sequences. The tree topology of Betacoronavirus is remarkably consistent with biologist's systematics. Because the tree construction contains enough information about virus mutants, it is suitable to study the evolutionary relationship between novel coronavirus mutants transmitted among humans. The emergences of 14 kinds of main mutants are studied and these strains can be classified as eight bifurcations of the phylogenetic tree. It is found that there exist three types of virus mutati…
The emergence of new variants of SARS-CoV-2 is a major concern given their potential impact on the transmissibility and pathogenicity of the virus as well as the efficacy of therapeutic interventions. Here, we predict the mutability of all positions in SARS-CoV-2 protein domains to forecast the appearance of unseen variants. Using sequence data from other coronaviruses, pre-existing to SARS-CoV-2, we build statistical models that do not only capture amino-acid conservation but more complex patterns resulting from epistasis. We show that these models are notably superior to conservation profile…
A method of Transitional Automorphic Mapping of the Genome on Itself (TAMGI) is aimed at combining detection and reconstruction of correlational and quasi-periodic motifs in the viral genomic RNA/DNA sequences. The motifs reconstructed by TAMGI are robust with respect to indels and point mutations and can be tried as putative therapeutic targets. We developed and tested the relevant theory and statistical criteria for TAMGI applications. The applications of TAMGI are illustrated by the study of motifs in the genomes of the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2…
