No abstract

D614G spike glycoprotein (sgp) mutation in rapidly spreading severe acute respiratory syndrome coronavirus‐2 (SARS‐COV‐2) is associated with enhanced fitness and higher transmissibility in new cases of COVID‐19 but the underlying mechanism is unknown. Here, using atomistic simulation, a plausible mechanism has been delineated. In G614 sgp but not wild type, increased D(G)614‐T859 Cα‐distance within 65 ns is interpreted as S1/S2 protomer dissociation. Overall, ACE2‐binding, post‐fusion core, open‐state and sub‐optimal antibody‐binding conformations were preferentially sampled by the G614 mutant, but not wild type. Furthermore, in the wild type, only one of the three sgp chains has optimal communication route between residue 614 and the receptor‐binding domain (RBD); whereas, two of the three chains communicated directly in G614 mutant. These data provide evidence that D614G sgp mutant is more available for receptor binding, cellular invasion and reduced antibody interaction; thus, providing framework for enhanced fitness and higher transmissibility in D614G SARS‐COV‐2 mutant.

COVID‐19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over‐reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re‐evaluate the only area with strategic advantage; phytotherapy. One of the many plants with previous antiviral potency is against RNA viruses is Aframomum melegueta. In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS‐COV‐2 targets including 3C‐like proteinase (Mpro/3CLpro), 2′‐O‐ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface. Silica‐gel column partitioning of A. melegueta fruit/seed resulted in 6 fractions tested against furin activity. Diarylheptanoid (Letestuianin A), phenylpropanoid (4‐Cinnamoyl‐3‐hydroxy‐spiro[furan‐5,2′‐(1′H)‐indene]‐1′,2,3′(2′H,5H)‐trione), flavonoids (Quercetin, Apigenin and Tectochrysin) have been identified as high‐binding compounds to SARS‐COV‐2 targets in a polypharmacology manner. Di‐ethyl‐ether (IC50 = 0.03 mg/L), acetone (IC50 = 1.564 mg/L), ethyl‐acetate (IC50 = 0.382 mg/L) and methanol (IC50 = 0.438 mg/L) fractions demonstrated the best inhibition in kinetic assay while DEF, ASF and MEF completely inhibited furin‐recognition sequence containing Ebola virus‐pre‐glycoprotein. In conclusion, A. melegueta and its secondary metabolites have potential for addressing the therapeutic needs of African population during the COVID‐19 pandemic.

The results of this study support that flavonoids may modulate the expression of GLP-1 and its release via TGR5. This finding may underscore its anti-diabetic potency.

The emergence and wide dissemination of drug-resistant malarial parasites underscore the need to prevent post-transfusion malaria. In Nigeria, as in most of sub-Saharan Africa, however, blood donors are not routinely screened for malarial infection. Recently, 391 consecutive potential blood donors in a malaria-endemic area of south-western Nigeria were each checked for malarial parasitaemia using three methods: microscopy (all samples), OptiMAL (315 samples) and/or the Clinotech Malaria Cassette (142 samples). OptiMAL detects parasite-specific lactate dehydrogenase whereas the Clinotech test detects the surface proteins of merozoites and sporozoites. Microscopy revealed parasitaemias in 79 (20.2%) of the potential donors, the levels of parasitaemia varying from 34 to 6289 asexual parasites/microl (mean=445/microl). The prevalence of malarial parasitaemia, as detected by microscopy, was significantly higher during the rainy season than in the dry season (27.3% v. 5.5%; P<0.0001). There was no significant association between patent parasitaemia and fever (i.e. an axillary temperature > or =37.5 degrees C), blood group, gender or anaemia. The corresponding prevalences of malarial parasitaemia detected using the rapid diagnostic tests were 3.8% (12/315) for OptiMAL and 57.8% (82/142) for the Clinotech. With the results of the microscopy used as the 'gold standard', OptiMAL gave a sensitivity of only 16.0% but a specificity of 98.5%. The corresponding values for the Clinotech tests were 69.2% and 50.0%, respectively. It would clearly be beneficial to include screening for malaria parasitaemia in the routine investigation of potential blood donors in Nigeria, especially during the rainy season, when the risk of transfusion-transmitted malaria appears relatively high.