Alkharsah, K. R. | bioRxiv Science

bioRxiv2025

Q1020R in the spike proteins of MERS-CoV from Arabian camels and recent human cases confers resistance against soluble human DPP4

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a pre-pandemic coronavirus that is transmitted from camels, the natural reservoir, to humans and can cause severe disease. MERS cases have been documented in Arabia but not Africa, although the virus is circulating in both Arabian and African camels. Further, evidence has been provided that viruses in African camels might have a reduced capacity to cause disease. However, the underlying determinants are incompletely understood. Here, employing pseudotyped particles as model systems for MERS-CoV entry into cells, we compared cell entry of viruses from African and Arabian camels and its inhibition. We show that viruses found in Arabian camels and recent human cases are less susceptible to inhibition by human soluble DPP4 (sDPP4) than viruses from African camels, although both enter human cells efficiently and are comparably sensitive to inhibition by IFITM proteins and neutralizing antibodies. Furthermore, relative resistance to soluble DPP4 was linked to mutation Q1020R, present in the spike proteins of recent Arabian but not African viruses. These results support the concept that soluble DPP4 might constitute a natural barrier against human infection that is more efficiently overcome by viruses currently circulating in Arabian camels than those in African camels. IMPORTANCEMERS-CoV is an emerging virus that can cause severe lung disease, MERS, and is transmitted from camels to humans. Although MERS-CoV infects camels in both Africa and Arabia, MERS cases have only been documented in Arabia for reasons that remain incompletely understood. Here, we provide evidence that viruses recently circulating in Arabian camels and causing human infections are less susceptible to inhibition by human sDPP4 - a secreted version of the viral receptor that is present in various bodily fluids. Furthermore, we link sDPP4 resistance to mutation Q1020R in the spike protein of these viruses. These results suggest that viruses currently circulating in Arabian camels are better equipped to overcome a natural barrier to infection, sDPP4, than those circulating in African camels.

microbiology↗

bioRxiv2021

Gut microbiota analyses of Saudi populations for type 2 diabetes-related phenotypes reveals significant association

Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as T2D. To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2Dparticipants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic participants compared to non-diabetic participants, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures. Author summaryThe rates of Type 2 diabetes (T2D) in Saudi Arabia have risen dramatically in the last several decades due to socio-economic changes resulting in changes in dietary and sedentary lifestyles. This emergence has grown more rapidly and affects larger proportions of the population with estimates of T2D prevalence impacting 25% of the population. There is a paucity of microbiome data from Middle Eastern populations, and previous studies have been conducted on small sample sizes. Here we report on the first-ever characterization of gut microbiota T2D versus non-T2D and largest microbiome study ever conducted in a Middle Eastern country. The datasets from this study are important to create a regional reference T2D-microbiome catalogue which will propel the understanding of regional gut flora which are associated with T2D development. Based on T2D status and quantified glucose levels of Middle Eastern participants, relatively stable differences in stool composition were observed by differential abundance and alpha diversity measures. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic.

microbiology↗