scholarly journals 1’-Ribose Cyano Substitution Allows Remdesivir to Effectively Inhibit Nucleotide Addition and Proofreading during SARS-CoV-2 Viral RNA Replication

2021 ◽  
Author(s):  
Lu Zhang ◽  
Dong Zhang ◽  
Xiaowei Wang ◽  
Congmin Yuan ◽  
Yongfang Li ◽  
...  
Keyword(s):  
Global Health ◽  
Rna Replication ◽  
Interventional Therapy ◽  
Viral Rna ◽  
Effective Inhibitor ◽  
Health Crisis ◽  
Nucleotide Addition

COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. Remdesivir is one effective inhibitor for SARS-CoV-2 viral RNA replication. It supersedes other NTP...

scholarly journals Role of 1’-Ribose Cyano Substitution for Remdesivir to Effectively Inhibit Nucleotide Addition and Proofreading in SARS-CoV-2 Viral RNA Replication

2020 ◽  
Author(s):  
Lu Zhang ◽  
Dong Zhang ◽  
Xiaowei Wang ◽  
Congmin Yuan ◽  
Yongfang Li ◽  
...  
Keyword(s):  
Rational Design ◽  
Molecular Mechanisms ◽  
Cyano Group ◽  
Rna Replication ◽  
Viral Rna ◽  
Upstream Site ◽  
Health Crisis ◽  
Nucleotide Addition

ABSTRACTCOVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is a promising but challenging drug target due to its intrinsic proofreading exoribonuclease (ExoN). Remdesivir targeting SARS-CoV-2 RdRp exerts high drug efficacy in vitro and in vivo. However, its underlying inhibitory mechanisms remain elusive. Here, we performed all-atom molecular dynamics simulations with an accumulated simulation time of 24 microseconds to elucidate the molecular mechanisms underlying the inhibitory effects of Remdesivir. We found that Remdesivir’s 1’-cyano group of possesses the dual role of inhibiting nucleotide addition and proofreading. The presence of its polar 1’-cyano group at an upstream site in RdRp causes instability and hampers RdRp translocation. This leads to a delayed chain termination of RNA extension, which may also subsequently reduce the likelihood for Remdesivir to be cleaved by ExoN acting on the 3’-terminal nucleotide. In addition, our simulations suggest that Remdesivir’s 1’-cyano group can also disrupt the cleavage active site of ExoN via steric interactions, leading to a further reduced cleavage efficiency. Our work provides plausible molecular mechanisms on how Remdesivir inhibits viral RNA replication and may guide rational design for new treatments of COVID-19 targeting viral replication.

Obesity – a global health crisis

2014 ◽  
pp. 9-10
Author(s):  
Hannah Brinsden
Keyword(s):  
Global Health ◽  
Health Crisis

scholarly journals 2020 FDA TIDES (Peptides and Oligonucleotides) Harvest

2021 ◽  
Vol 14 (2) ◽  
pp. 145
Author(s):  
Othman Al Musaimi ◽  
Danah Al Shaer ◽  
Fernando Albericio ◽  
Beatriz de la Torre
Keyword(s):  
Adverse Effects ◽  
Global Health ◽  
Drug Administration ◽  
Mode Of Action ◽  
Chemical Structure ◽  
Food And Drug Administration ◽  
Health Crisis ◽  
New Drug ◽  
Target Mode ◽  
The Us

2020 has been an extremely difficult and challenging year as a result of the coronavirus disease 2019 (COVID-19) pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Administration (FDA) has approved 53 new drug entities, six of which fall in the peptides and oligonucleotides (TIDES) category. The number of authorizations for these kinds of drugs has been similar to that of previous years, thereby reflecting the consolidation of the TIDES market. Here, the TIDES approved in 2020 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects.

scholarly journals Medicines dispensing practice during the era of COVID-19 pandemic: a commentary

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gemmechu Hasen ◽  
Rashed Edris ◽  
Gadisa Chala ◽  
Yesuneh Tefera ◽  
Hawi Hussen ◽  
...  
Keyword(s):  
Global Health ◽  
Turning Point ◽  
Healthcare Systems ◽  
Pharmacy Services ◽  
Resource Limited Settings ◽  
Health Crisis ◽  
Drug Dispensing ◽  
Resource Limited ◽  
Retail Outlets ◽  
Jimma Town

AbstractThe coronavirus disease 19 (COVID-19) pandemic is putting a huge strain on healthcare systems and is a turning point for the beginning of a global health crisis of an unprecedented condition. As such, the provision of quality pharmacy services particularly, dispensing practice with pre-existing challenges in resource-limited settings is a grave concern in the era of the COVID-19 pandemic. Thus, in this commentary we described the pattern of dispensing practice in the midst of the COVID-19 pandemic by evaluating the current condition of drug dispensing practice in drug retail outlets of Jimma Town.

scholarly journals The Implications of the COVID-19 Pandemic on Religious Exercise: Preliminary Remarks

Laws ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 44
Author(s):  
Adelaide Madera
Keyword(s):  
Global Health ◽  
Health And Safety ◽  
Fundamental Rights ◽  
Special Issue ◽  
Health Crisis ◽  
Personal Lives ◽  
Regulatory Frameworks ◽  
Starting Point ◽  
Legal Contexts

Since 2020, the spread of COVID-19 has had an overwhelming impact not only on our personal lives, but also on domestic regulatory frameworks. Influential academics have strongly underlined that, in times of deep crisis, such as the current global health crisis, the long-term workability of legal systems is put to a severe test. In this period, in fact, the protection of health has been given priority, as a precondition that is orientating many current legal choices. Such an unprecedented health emergency has also raised a serious challenge in terms of fundamental rights and liberties. Several basic rights that normally enjoy robust protection under constitutional, supranational, and international guarantees, have experienced a devastating “suspension” for the sake of public health and safety, thus giving rise to a vigorous debate concerning whether and to what extent the pandemic emergency justifies limitations on fundamental rights. The present paper introduces the Special Issue on “The crisis of the religious freedom during the age of COVID-19 pandemic”. Taking as a starting point the valuable contributions of the participants in the Special Issue, it explores analogous and distinctive implications of the COVID-19 pandemic in different legal contexts and underlines the relevance of cooperation between religious and public actors to face a global health crisis.

scholarly journals Heat Shock Protein 72 Is Associated with the Hepatitis C Virus Replicase Complex and Enhances Viral RNA Replication

2010 ◽  
Vol 285 (36) ◽  
pp. 28183-28190 ◽  
Author(s):  
Yin-Ju Chen ◽  
Yu-Hsuan Chen ◽  
Lu-Ping Chow ◽  
Ya-Hui Tsai ◽  
Pei-Hong Chen ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Rna Replication ◽  
Viral Rna ◽  
Heat Shock Protein 72 ◽  
Replicase Complex

Hepatitis Delta Virus cDNA Monomer Can Be Used in Transfection Experiments to Initiate Viral RNA Replication

Virology ◽  
1993 ◽  
Vol 197 (1) ◽  
pp. 137-142 ◽  
Author(s):  
Fei-Ping Tai ◽  
Pei-Jer Chen ◽  
Fu-Lin Chang ◽  
Ding-Shinn Chen
Keyword(s):  
Hepatitis Delta Virus ◽  
Rna Replication ◽  
Viral Rna ◽  
Hepatitis Delta ◽  
Virus Cdna ◽  
Delta Virus
Sign in / Sign up

Export Citation Format

Share Document