02586naa a2200397 a 450000100080000000500110000800800410001910000200006024501460008026000090022650000340023552014550026965300140172465300250173865300190176365300080178265300110179065300200180165300150182170000210183670000180185770000150187570000200189070000190191070000170192970000240194670000220197070000160199270000150200870000250202370000170204870000150206570000220208070000210210277300650212321742612025-03-27       2025    bl uuuu     u00u1 u    #d1 aORFANOUDAKI, M.  aIsolation and structure elucidation of Dm-CVNH, a new cyanovirin-N homolog with activity against SARS-CoV-2 and HIV-1.h[electronic resource]  c2025  aNa publicação: Elibio Rech.  aAn anti-HIV screen of natural product extracts resulted in the discovery of a new antiviral protein through bioassay-guided fractionation of an aqueous extract of the ascidian Didemnum molle. The protein was sequenced through a combination of tandem mass spectroscopy and N-terminal Edman degradation of peptide fragments after a series of endoproteinase digestions. The primary amino acid sequence and disulfide bonding pattern of the 102-amino acid protein were closely related to the antiviral protein cyanovirin-N (CV-N). This new CV-N homolog was named Dm-CVNH. Alphafold2 prediction resulted in a tertiary structure, highly similar to CV-N, comprised of two symmetrically related domains that contained five β-strands and two α-helical turns each. Dm-CVNH showed specificity for high mannose and oligomannose structures, bound to HIV-1 gp-120 and potently inactivated HIV in neutralization assays (EC50 of 0.95 nM). Dm-CVNH inhibited infection in a SARS-CoV-2 live virus assays and was shown to bind to the S1 domain of SARS-CoV-2 Spike glycoprotein. Dm-CVNH behaved in a manner similar to CV-N, binding with a 2:1 stoichiometry to Spike (both to WH-1 and Omicron variants) and preferring the Omicron variant (Kd 42 nM) to original WH-1 (Kd = 89 nM) Spike. This sensitivity to emergent strains was mirrored in viral neutralization assays where Dm-CVNH potently inhibited the infection of Omicron strains XBB.1.16 and JN.1 (IC50 = 11–18 nM).  aAntiviral  aCyanovirin-N homolog  aDidemnum molle  aHIV  aLectin  aNatural product  aSARS-CoV-21 aKRUMPE, L. R. H.1 aSHENOY, S. R.1 aWILSON, J.1 aGUSZCZYNSKI, T.1 aHENRICH, C. J.1 aTEMME, J. S.1 aGILDERSLEEVE, J. C.1 aMOLINA-MOLINA, E.1 aERKIZIA, I.1 aBLANCO, J.1 aIZQUIERDO-USEROS, N.1 aMONTIERO, F.1 aTANURI, A.1 aRECH FILHO, E. L.1 aO’KEEFE, B. R.  tJournal of Biological Chemistrygv. 301, n. 3, 108319, 2025.