Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection.

The clinical presentation of COVID-19 shows high variability among individuals, which is partly due to genetic factors. The OAS1/2/3 cluster has been found to be strongly associated with COVID-19 severity. We examined this locus in the Moroccan population for the occurrence of the critical variant rs10774671 and its respective haplotype blocks. The frequency of single-nucleotide polymorphisms (SNPs) in the cluster of OAS immunity genes in 157 unrelated individuals of Moroccan origin was determined using an in-house exome database. OAS1 exon 6 of 71 SARS-CoV-2-positive individuals with asymptomatic/mild disease and 74 with moderate/severe disease was sequenced by the Sanger method. The genotypic, allelic, and haplotype frequencies of three SNPs were compared between these two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was found to be 40.4%, which is similar to that found in Europeans. However, it was found equally in both the Neanderthal GGG haplotype and the African GAC haplotype, with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008, respectively). Surprisingly, in men with the Berber-specific uniparental markers, the African haplotype was absent, while the prevalence of the Neanderthal haplotype was similar to that in Europeans. The protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as a stepping-stone for the passage of hominids to other continents.

Affinity comparison of different THCA synthase to CBGA using modeling computational approaches.

The Δ(9-)Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by Δ(1-) Tetrahydrocannabinolic acid synthase (THCA) which catalyzes the oxidative cyclization of cannabigerolic acid (CBGA) the precursor of the THCA. In this study, we were interested by the three dimensional structure of THCA synthase protein. Generation of models were done by MODELLER v9.11 and homology modeling with Δ1-tetrahydrocannabinolic acid (THCA) synthase X ray structure (PDB code 3VTE) on the basis of sequences retrieved from GenBank. Procheck, Errat, and Verify 3D tools were used to verify the reliability of the six 3D models obtained, the overall quality factor and the Prosa Z-score were also used to check the quality of the six modeled proteins. The RMSDs for C-alpha atoms, main-chain atoms, side-chain atoms and all atoms between the modeled structures and the corresponding template ranged between 0.290 Å-1.252 Å, reflecting the good quality of the obtained models. Our study of the CBGA-THCA synthase docking demonstrated that the active site pocket was successfully recognized using computational approach. The interaction energy of CBGA computed in 'fiber types' proteins ranged between -4.1 95 kcal/mol and -5.95 kcal/mol whereas in the 'drug type' was about -7.02 kcal/mol to -7.16 kcal/mol, which maybe indicate the important role played by the interaction energy of CBGA in the determination of the THCA level in Cannabis Sativa L. varieties. Finally, we have proposed an experimental design in order to explore the binding energy source of ligand-enzyme in Cannabis Sativa and the production level of the THCA in the absence of any information regarding the correlation between the enzyme affinity and THCA level production. This report opens the doors to more studies predicting the binding site pocket with accuracy from the perspective of the protein affinity and THCA level produced in Cannabis Sativa.