Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.


Omotuyi IO(1)(2), Nash O(3), Ajiboye BO(4), Olumekun VO(5), Oyinloye BE(4)(6), Osuntokun OT(7), Olonisakin A(7), Ajayi AO(8), Olusanya O(9), Akomolafe FS(10), Adelakun N(2).
Author information:
(1)Chemo-Genomics Research Unit, Department of Biochemistry, Adekunle Ajasin University, Akungba, Nigeria.
(2)Chemoinformatics Unit, Mols & Sims, Ado Ekiti, Nigeria.
(3)Center for Genomics Research and Innovation, National Biotechnology Development Agency, Abuja, Nigeria.
(4)Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, Ado Ekiti, Nigeria.
(5)Department of Plant Science and Biotechnology, Adekunle Ajasin University, Akungba, Nigeria.
(6)Biotechnology and Structural Biology
(BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa.
(7)Department of Chemical Sciences, Adekunle Ajasin University, Akungba, Nigeria.
(8)Department of Microbiology, Adekunle Ajasin University, Akungba, Nigeria.
(9)Department of Biochemistry, Faculty of Life Sciences, University of Benin, Benin City, Nigeria.
(10)Department of Biochemistry, Ekiti State University, Ado Ekiti, Nigeria.


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.