On the mechanisms of bananin activity against severe acute respiratory syndrome coronavirus.
In a previous study, severe acute respiratory syndrome coronavirus (SARS-CoV) was cultured in the presence of bananin, an effective adamantane-related molecule with antiviral activity. In the present study, we show that all bananin-resistant variants exhibit mutations in helicase and membrane protein, although no evidence of bananin interference on their mutual interaction has been found. A structural analysis on protein sequence mutations found in SARS-CoV bananin-resistant variants was performed. The S259/L mutation of SARS-CoV helicase is always found in all the identified bananin-resistant variants, suggesting a primary role of this mutation site for bananin activity. From a structural analysis of SARS-CoV predicted helicase structure, S259 is found in a hydrophilic surface pocket, far from the enzyme active sites and outside the helicase dimer interface. The S/L substitution causes a pocket volume reduction that weakens the interaction between bananin and SARS-CoV mutated helicase, suggesting a possible mechanism for bananin antiviral activity.
Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Zai
Z
Wang
Jian-Dong
JD
Huang
Kin-Ling
KL
Wong
Pei-Gang
PG
Wang
Hao-Jie
HJ
Zhang
Julian A
JA
Tanner
Ottavia
O
Spiga
Andrea
A
Bernini
Bo-Jian
BJ
Zheng
Neri
N
Niccolai
D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D000086862:Coronavirus M Proteins; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008562:Membrane Glycoproteins / Q000235:genetics; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D020836:Protein Structure, Quaternary; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000235:genetics*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy; D064370:Spike Glycoprotein, Coronavirus; D055672:Static Electricity; D014759:Viral Envelope Proteins / Q000235:genetics; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014867:Water / Q000737:chemistry
D000086862:Coronavirus M Proteins; C000706237:M protein, SARS-CoV; D008562:Membrane Glycoproteins; D011725:Pyridines; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C487581:bananin; D014867:Water; D004265:DNA Helicases; D020365:RNA Helicases; D000218:Adamantane