In Silico Design of an Oseltamivir Derivative with Increased Affinity against Wild-Type and Mutant Variants of Neuraminidase and Hemagglutinin of Influenza A H1N1 Virus
Chem Biodivers. 2023 Jun 28:e202201077. doi: 10.1002/cbdv.202201077. Online ahead of print.ABSTRACTAntiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific ...
Source: Chemistry and Biodiversity - June 28, 2023 Category: Biochemistry Authors: Garc ía-Machorro Jazmin Mirzaeicheshmeh Elaheh Fragoso-V ázquez Manuel Jonathan Bello Martiniano M éndez-Luna David Le ón-Cardona Alám Correa-Basurto Jos é Source Type: research
In Silico Design of an Oseltamivir Derivative with Increased Affinity against Wild-Type and Mutant Variants of Neuraminidase and Hemagglutinin of Influenza A H1N1 Virus
Chem Biodivers. 2023 Jun 28:e202201077. doi: 10.1002/cbdv.202201077. Online ahead of print.ABSTRACTAntiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific ...
Source: Chemistry and Biodiversity - June 28, 2023 Category: Biochemistry Authors: Garc ía-Machorro Jazmin Mirzaeicheshmeh Elaheh Fragoso-V ázquez Manuel Jonathan Bello Martiniano M éndez-Luna David Le ón-Cardona Alám Correa-Basurto Jos é Source Type: research
Exploring the inhibition of the soluble lytic transglycosylase Cj0843c of Campylobacter jejuni via targeting different sites with different scaffolds
This article is protected by copyright. All rights reserved. (Source: Protein Science)
Source: Protein Science - May 21, 2023 Category: Biochemistry Authors: Vijay Kumar,
Jacob Boorman,
William J. Greenlee,
Ximin Zeng,
Jun Lin,
Focco van den Akker Tags: ARTICLE Source Type: research
Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors
Eur J Med Chem. 2023 Apr 24;255:115410. doi: 10.1016/j.ejmech.2023.115410. Online ahead of print.ABSTRACTThe influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses. A neuraminidase on the virus's surface serves a vital function in viral propogation by assisting in the release of viruses from infected host cells. Neuraminidase inhibitors are the backbone in stoping such virus prop...
Source: European Journal of Medicinal Chemistry - April 30, 2023 Category: Chemistry Authors: Yogesh Yadav Rajdeep Tyagi Ramesh Kumar Ram Sagar Source Type: research
Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors
Eur J Med Chem. 2023 Apr 24;255:115410. doi: 10.1016/j.ejmech.2023.115410. Online ahead of print.ABSTRACTThe influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses. A neuraminidase on the virus's surface serves a vital function in viral propogation by assisting in the release of viruses from infected host cells. Neuraminidase inhibitors are the backbone in stoping such virus prop...
Source: European Journal of Medicinal Chemistry - April 30, 2023 Category: Chemistry Authors: Yogesh Yadav Rajdeep Tyagi Ramesh Kumar Ram Sagar Source Type: research
Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors
Eur J Med Chem. 2023 Apr 24;255:115410. doi: 10.1016/j.ejmech.2023.115410. Online ahead of print.ABSTRACTThe influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses. A neuraminidase on the virus's surface serves a vital function in viral propogation by assisting in the release of viruses from infected host cells. Neuraminidase inhibitors are the backbone in stoping such virus prop...
Source: European Journal of Medicinal Chemistry - April 30, 2023 Category: Chemistry Authors: Yogesh Yadav Rajdeep Tyagi Ramesh Kumar Ram Sagar Source Type: research
Viruses, Vol. 15, Pages 1056: Targeting the Human Influenza a Virus: The Methods, Limitations, and Pitfalls of Virtual Screening for Drug-like Candidates Including Scaffold Hopping and Compound Profiling
In this study, we describe the input data and processing steps to find antiviral lead compounds by a virtual screen. Two-dimensional and three-dimensional filters were designed based on the X-ray crystallographic structures of viral neuraminidase co-crystallized with substrate sialic acid, substrate-like DANA, and four inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir). As a result, ligand–receptor interactions were modeled, and those necessary for binding were utilized as screen filters. Prospective virtual screening (VS) was carried out in a virtual chemical library of over half a million small...
Source: Viruses - April 26, 2023 Category: Virology Authors: Thomas Scior Karina Cuanalo-Contreras Angel A. Islas Ygnacio Martinez-Laguna Tags: Article Source Type: research
Lessons from resistance analysis in clinical trials of IV zanamivir
In this study ten resistance substitutions, two of which were treatment emergent, were detected by NGS that otherwise would not have been detectable by Sanger sequencing. None of the substitutions were present at any other timepoints analysed. The effect these mutations have on clinical response is difficult to characterize; in fact, all patients from which these variants were isolated had a successful clinical outcome and the effect on clinical response was therefore likely minimal. Although NGS is becoming a routine method for nucleic acid sequencing and will detect substitutions previously undetected by Sanger sequencin...
Source: Virus Research - January 7, 2023 Category: Virology Authors: Phillip J Yates Nalini Mehta Helen A Watson Amanda F Peppercorn Source Type: research
Lessons from resistance analysis in clinical trials of IV zanamivir
In this study ten resistance substitutions, two of which were treatment emergent, were detected by NGS that otherwise would not have been detectable by Sanger sequencing. None of the substitutions were present at any other timepoints analysed. The effect these mutations have on clinical response is difficult to characterize; in fact, all patients from which these variants were isolated had a successful clinical outcome and the effect on clinical response was therefore likely minimal. Although NGS is becoming a routine method for nucleic acid sequencing and will detect substitutions previously undetected by Sanger sequencin...
Source: Virus Research - January 7, 2023 Category: Virology Authors: Phillip J Yates Nalini Mehta Helen A Watson Amanda F Peppercorn Source Type: research
Lessons from resistance analysis in clinical trials of IV zanamivir
In this study ten resistance substitutions, two of which were treatment emergent, were detected by NGS that otherwise would not have been detectable by Sanger sequencing. None of the substitutions were present at any other timepoints analysed. The effect these mutations have on clinical response is difficult to characterize; in fact, all patients from which these variants were isolated had a successful clinical outcome and the effect on clinical response was therefore likely minimal. Although NGS is becoming a routine method for nucleic acid sequencing and will detect substitutions previously undetected by Sanger sequencin...
Source: Virus Research - January 7, 2023 Category: Virology Authors: Phillip J Yates Nalini Mehta Helen A Watson Amanda F Peppercorn Source Type: research
Lessons from resistance analysis in clinical trials of IV zanamivir
In this study ten resistance substitutions, two of which were treatment emergent, were detected by NGS that otherwise would not have been detectable by Sanger sequencing. None of the substitutions were present at any other timepoints analysed. The effect these mutations have on clinical response is difficult to characterize; in fact, all patients from which these variants were isolated had a successful clinical outcome and the effect on clinical response was therefore likely minimal. Although NGS is becoming a routine method for nucleic acid sequencing and will detect substitutions previously undetected by Sanger sequencin...
Source: Virus Research - January 7, 2023 Category: Virology Authors: Phillip J Yates Nalini Mehta Helen A Watson Amanda F Peppercorn Source Type: research
Molecules, Vol. 27, Pages 7797: Essential Oils and Their Compounds as Potential Anti-Influenza Agents
eji
Essential oils (EOs) are chemical substances, mostly produced by aromatic plants in response to stress, that have a history of medicinal use for many diseases. In the last few decades, EOs have continued to gain more attention because of their proven therapeutic applications against the flu and other infectious diseases. Influenza (flu) is an infectious zoonotic disease that affects the lungs and their associated organs. It is a public health problem with a huge health burden, causing a seasonal outbreak every year. Occasionally, it comes as a disease pandemic with unprecedentedly high hospitalization and mortality...
Source: Molecules - November 12, 2022 Category: Chemistry Authors: Ayodeji Oluwabunmi Oriola Adebola Omowunmi Oyedeji Tags: Review Source Type: research
Binding of Glycans to the SARS CoV-2 Spike Protein, an Open Question: NMR Data on Binding Site Localization, Affinity, and Selectivity
Chemistry. 2022 Sep 26. doi: 10.1002/chem.202202614. Online ahead of print.ABSTRACTWe have used NMR experiments to explore binding of selected glycans and glycomimetics to the SARS CoV-2 spike glycoprotein (S-protein) and to its receptor binding domain (RBD). STD NMR experiments confirm binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the mM range. The absence of STD effects for sialoglycans in the presence of the Omicron/BA.1 S-protein reflects a loss of binding as a result of S-protein evolution. Likewise, no STD effects are observed for the deletion mutant...
Source: Chemistry - September 26, 2022 Category: Chemistry Authors: Thorben Maass George Ssebyatika Marlene Br ückner Lea Breckwoldt Thomas Krey Alvaro Mallagaray Thomas Peters Martin Frank Robert Creutznacher Source Type: research
Molecules, Vol. 27, Pages 5920: In Silico Studies Reveal Peramivir and Zanamivir as an Optimal Drug Treatment Even If H7N9 Avian Type Influenza Virus Acquires Further Resistance
dekar
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 tha...
Source: Molecules - September 12, 2022 Category: Chemistry Authors: Edita Sarukhanyan Tipack Ayothyapattanam Shanmugam Thomas Dandekar Tags: Article Source Type: research
Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Comput Biol Chem. 2022 Aug 28;101:107764. doi: 10.1016/j.compbiolchem.2022.107764. Online ahead of print.ABSTRACTRecently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replic...
Source: Computational Biology and Chemistry - September 1, 2022 Category: Bioinformatics Authors: Thitiya Boonma Nattharuja Soikudrua Bodee Nutho Thanyada Rungrotmongkol Nadtanet Nunthaboot Source Type: research
