A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

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

IntroductionThis study aims to determine the Acinetobacter sp clinical isolates frequency and its antibiotic susceptibility pattern by comparing results obtained from the Intensive Care Units (ICUs) to that of other units at the Mohammed V Military Teaching Hospital in Rabat.MethodsThis is a retrospective study over a 2-years period where we collected all clinical isolates of Acinetobacter sp obtained from samples for infection diagnosis performed on hospitalized patients between 2012 to 2014.ResultsDuring the study period, 441 clinical and non-repetitive isolates of Acinetobacter sp were collected representing 6.94% of all bacterial clinical isolates (n = 6352) and 9.6% of Gram negative rods (n = 4569). More than a half of the isolates were from the ICUs and were obtained from 293 infected patients of which 65, 2% (191 cases) were males (sex ratio = 1.9) and the median age was 56 years (interquartile range: 42-68 years). Acinetobacter clinical isolates were obtained from respiratory samples (44.67%) followed by blood cultures (14.51%). The resistance to ciprofloxacin, ceftazidime, piperacillin / tazobactam, imipenem, amikacin, tobramycin, netilmicin, rifampicin and colistin was respectively 87%, 86%, 79%, 76%; 52%, 43%, 33% 32% and 1.7%. The difference in resistance between the ICUs and the other units was statistically significant (p <0.05) except for colistin, tetracycline and rifampicin.ConclusionThis paper shows that solving the problem of prevalence and high rate of multidrug resistant Acinetobacter infection which represents a therapeutic impasse, requires the control of the hospital environment and optimizing hands hygiene and antibiotics use in the hospital.

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 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.