Enteroviruses (EVs) infect millions of people annually. EV infections can be asymptomatic or symptomatic with conditions ranging from mild illnesses to serious diseases such as dilated cardiomyopathy. A causal relationship between EV infections and type 1 diabetes mellitus (T1DM) has been heavily debated, with some studies suggesting that this relationship is not yet conclusive and requires additional evidence, whereas others strongly argue for this correlation. While this relationship is well investigated in some developed countries like the USA and Finland, it is understudied or neglected in other countries like Russia for many reasons such as the low incidence of T1DM. Although the Middle East and North Africa (MENA) are highly affected by T1DM, the role of EVs in the disease in MENA has not been investigated extensively. Therefore, we aimed to address the relationship between T1DM and EVs in MENA and other regions globally.

The role of enteroviruses in type 1 diabetes has long been suspected. A lower risk of type 1 diabetes is associated with breastfeeding, which could be due to a protective effect against enteroviruses. The neutralizing activity of breast milk against CVB4, a representative of enteroviruses was investigated in this study in vitro. Breast milk was cytotoxic to Hep-2 cells up to a dilution of 1/32, whereas the aqueous fraction obtained after centrifugation was not cytotoxic; although it inhibited the cytopathic effect of CVB4 on Hep-2 cell monolayers. The anti-CVB4 neutralizing activity of aqueous fractions of breast milk from 49 donors living in Northern France and 15 donors living in Congo, where enteroviral infections are more prevalent, were determined. The levels of colostrum activity expressed as titre ranged from <2 to 32 in 36% of the donors from France whereas they were >128 in every donor from Congo. Pasteurized colostrum had a lower anti-CVB4 activity compared to fresh samples (P < 0.0001, n = 49). The treatment of colostrum samples with jacalin-coated beads that bind specifically to human IgA, showed that IgA plays a role in anti-CVB4 activity. There was no correlation between the neutralizing activities of breast milk and serum (P = 0.37, n = 25). The current study showed that the variations in anti-CVB4 activity in breast milk can be attributed to environmental and living conditions. Whether a low protective activity of breast milk against enteroviruses expose newborns to a higher risk of type 1 diabetes deserves further investigation.

The association between saliva anti-CV-B4 activity and disturbance of immune system in T1D patients deserves further investigation.

Traditional practitioners commonly use plant crude extracts to treat various diseases in patients with symptoms that can be seen during enterovirus infections. In this study, the antienteroviral activity of medicinal plants from the Republic of Congo has been evaluated in vitro. Through an ethnopharmacological approach, seven plants grouped into six families were identified. Aqueous and organic extracts of various organs from these plants were prepared. The organic extracts at subcytotoxic concentrations did not inhibit the cytopathic effect (CPE) induced by coxsackievirus (CV)B1-5, CVA6, poliovirus type 1, and enterovirus 71. The aqueous extract of Syzygium brazzavillense, but not those of other plants, inhibited the CPE induced by CVB3 and CVB4 at 30 µg/mL (CC 50 ; 2800 µg/mL, IC 50 ; 0.8 µg/mL) and by CVB2 and poliovirus type 1 at higher concentrations. When aqueous extract of this plant was mixed with CVB4, the replication of the virus was inhibited. In conclusion, aqueous extracts of Syzygium brazzavillense can inhibit the infection with CVB4 and other enteroviruses in vitro. The present ethnopharmacological investigation helped to identify a plant with potential properties useful to combat enterovirus infections. K E Y W O R D S antiviral activity, aqueous extracts, enterovirus, plant, Republic of Congo

There is an anti-CV-B4 activity in saliva of patients with type 1 diabetes that may be a useful marker to study the role of CV-B in the pathogenesis of the disease.