TY  - JOUR
A1  - Sarukhanyan, Edita
A1  - Shanmugam, Tipack Ayothyapattanam
A1  - Dandekar, Thomas
T1  - In silico studies reveal Peramivir and Zanamivir as an optimal drug treatment even if H7N9 avian type influenza virus acquires further resistance
JF  - Molecules
N2  - An epidemic of avian type H7N9 influenza virus, which took place in China in 2013, was enhanced by a naturally occurring R294K mutation resistant against Oseltamivir at the catalytic site of the neuraminidase. To cope with such drug-resistant neuraminidase mutations, we applied the molecular docking technique to evaluate the fitness of the available drugs such as Oseltamivir, Zanamivir, Peramivir, Laninamivir, L-Arginine and Benserazide hydrochloride concerning the N9 enzyme with single (R294K, R119K, R372K), double (R119_294K, R119_372K, R294_372K) and triple (R119_294_372K) mutations in the pocket. We found that the drugs Peramivir and Zanamivir score best amongst the studied compounds, demonstrating their high binding potential towards the pockets with the considered mutations. Despite the fact that mutations changed the shape of the pocket and reduced the binding strength for all drugs, Peramivir was the only drug that formed interactions with the key residues at positions 119, 294 and 372 in the pocket of the triple N9 mutant, while Zanamivir demonstrated the lowest RMSD value (0.7 Å) with respect to the reference structure.
KW  - H7N9 influenza virus
KW  - neuraminidase
KW  - mutation
KW  - binding pocket
KW  - molecular docking
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288240
SN  - 1420-3049
VL  - 27
IS  - 18
ER  - 
TY  - JOUR
A1  - Gupta, Shishir K.
A1  - Minocha, Rashmi
A1  - Thapa, Prithivi Jung
A1  - Srivastava, Mugdha
A1  - Dandekar, Thomas
T1  - Role of the pangolin in origin of SARS-CoV-2: an evolutionary perspective
JF  - International Journal of Molecular Sciences
N2  - After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron.
KW  - COVID-19
KW  - SARS-CoV-2
KW  - origin
KW  - evolution
KW  - intermediate host
KW  - pangolin
KW  - mutation
KW  - recombination
KW  - adaptation
KW  - transmission
KW  - comparative sequence analysis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285995
SN  - 1422-0067
VL  - 23
IS  - 16
ER  -