Large scale genomic analysis of 3067 SARS-1 CoV-2 genomes reveals a clonal geo-distribution 2 and a rich genetic variations of hotspots 3 mutations 4 Abstract 33In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, 34China, and became a global pandemic. Characterization of the genetic variants of SARS-35CoV-2 is crucial in following and evaluating it spread across countries. In this study, we 36 collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the 37 first three months after the onset of this virus. Using comparative genomics analysis, we 38 traced the profiles of the whole-genome mutations and compared the frequency of each 39 mutation in the studied population. The accumulation of mutations during the epidemic 40 period with their geographic locations was also monitored. The results showed 782 variant 41 sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles 42 revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot 43 mutations with a prevalence higher than 0.10 in this population and distributed in six 44 SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map 45 revealed certain genotypes specific to the geographic location. We also found co-occurring 46 mutations resulting in the presence of several haplotypes. Moreover, evolution over time 47We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists 52 all of the genetic variants of the SARS-CoV-2 genomes found in this study with 53 phylogeographic analysis around the world. 54 55 56

In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.

The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.

The Coronavirus disease 19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome.Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2.These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely.

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Here, we report the draft genome sequences of six severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. SARS-CoV-2 is responsible for the COVID-19 pandemic, which started at the end of 2019 in Wuhan, China. The isolates were obtained from nasopharyngeal swabs from Moroccan patients with COVID-19. Mutation analysis revealed the presence of the spike D614G mutation in all six genomes, which is widely present in several genomes around the world.

Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms.