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 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 December 24, 2019, to May 13, 2020, according to the GISAID database. Our analysis revealed the presence of 3,206 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 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 mutational frequency dissimilarity and intra-genomic divergence of SARS-CoV-2 could indicate that the SARS-CoV-2 is not yet adapted to its host. Unlike the influenza virus or HIV viruses, the low mutation rate of SARS-CoV-2 makes the development of an effective global vaccine very likely.

Africa’s 1.5 billion people are underrepresented in genomic databases. The African Genome Variation Project exclusively focuses on Sub-Saharan populations, making Morocco, located in North Africa, a valuable site for studying genetic diversity. Understanding genetic variation and customized therapy requires population-specific reference genomes. This study presents Phase 1 results from the Moroccan Genome Project (MGP), which sequenced 109 Moroccan genomes. We report over 27 million variants, including 1.4 million novel ones, of which 15,378 are highly prevalent in the Moroccan population. Furthermore, we propose a Moroccan Major Allele Reference Genome (MMARG), generated using high-coverage consensus sequences from the 109 whole genomes. This MMARG represents more accurately the Moroccan genetic variation than GRCh38. This baseline study also generates an informative genetic variation database that supports regional population-specific initiatives and precision medicine in Morocco and North Africa. The results stress the necessity of population-relevant data in Human genetic research.

Introduction: Immune checkpoint blockade targeting PD-1/PD-L1 has revolutionized cancer treatment; however, resistance remains a major clinical challenge. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA), a B7 family member with high expression in tumor-infiltrating lymphocytes of ovarian cancer, has emerged as a promising alternative target for immunotherapeutic intervention. Materials and Methods: We performed in silico screening of 9,397 DrugBank compounds against PD-L1 and VISTA using AutoDock Vina. The top candidates based on docking scores were assessed through 100 ns molecular dynamics simulations, and binding free energies were calculated via MM-PBSA. Results: DB15637, DB12867, and DB06744 showed the strongest PD-L1 binding affinities (−7.33 to −7.87 kcal/mol) with average RMSD values of 8.89 Å, 8.94 Å, and 7.57 Å, respectively. DB00321 exhibited the highest affinity for VISTA (−7.31 kcal/mol) with an RMSD of 6.18 Å, maintaining stable interactions with key residues throughout the simulation. Discussion: The identified compounds demonstrated favorable docking scores, dynamic stability, and binding free energies, suggesting their potential as PD-L1 and VISTA inhibitors. Dual checkpoint targeting could enhance antitumor immune responses in ovarian cancer, where both proteins contribute to immune evasion. Conclusion: This in silico study identified promising candidates for PD-L1 and VISTA inhibition. These findings provide a computational basis for further experimental validation to confirm their therapeutic potential in the treatment of ovarian cancer.