SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants DOI Creative Commons
Almu’atasim Khamees, Jamal Bani-Issa, Mazhar Salim Al Zoubi

et al.

Pathogens, Journal Year: 2022, Volume and Issue: 11(2), P. 275 - 275

Published: Feb. 20, 2022

COVID-19 is caused by a novel coronavirus (2019-nCoV), which was declared as pandemic after it emerged in China 2019. A vast international effort has been conducted to prevent and treat due its high transmissibility severe morbidity mortality rates, particularly individuals with chronic co-morbidities. In addition, polymorphic variants increased the need for proper vaccination overcome infectivity of new that are emerging across globe. Many treatment options have proposed more than 25 vaccines various stages development; however, infection peaks oscillating periodically, raises significant question about effectiveness prevention measures persistence this disease. review, we exploring most recent knowledge advances well 2019-nCoV possible mitigation one aggressive pandemics last centuries.

Language: Английский

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections DOI Creative Commons
Ren‐Jun Hsu,

Wei-Chieh Yu,

Guan-Ru Peng

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is by uncontrolled inflammation, aberrant immune response, cytokine storm, an imbalanced hyperactive system. The storm further results multiple organ failure lung immunopathology. Therefore, any potential treatments should focus on the direct elimination viral particles, prevention strategies, mitigation (hyperactive) This review focuses secretions innate adaptive responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, other chemokines. In addition to focus, we discuss immunotherapeutic approaches based relevant pathophysiological features, systemic response SARS-CoV-2, data from recent clinical trials experiments COVID-19-associated storm. Prompt use these cytokines as diagnostic markers aggressive management can help determine morbidity mortality. prophylaxis rapid appear significantly improve outcomes. For reasons, this study aims provide advanced information facilitate innovative strategies survive COVID-19 pandemic.

Language: Английский

Citations

106
Evolutionary and Structural Insights about Potential SARS-CoV-2 Evasion of Nirmatrelvir DOI
Kai S. Yang,

Sunshine Z. Leeuwon,

Shiqing Xu

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(13), P. 8686 - 8698

Published: June 22, 2022

The U.S. FDA approval of PAXLOVID, a combination therapy nirmatrelvir and ritonavir has significantly boosted our morale in fighting the COVID-19 pandemic. Nirmatrelvir is an inhibitor main protease (MPro) SARS-CoV-2. Since many SARS-CoV-2 variants that resist vaccines antibodies have emerged, concern acquired viral resistance to naturally arises. Here, possible mutations MPro confer evasion are analyzed discussed from both evolutionary structural standpoints. analysis indicates those will likely reside whole aa45–51 helical region residues including M165, L167, P168, R188, Q189. Relevant also been observed existing samples. Implications this fight against future drug-resistant development broad-spectrum antivirals as well.

Language: Английский

Citations

95
Oral GS-441524 derivatives: Next-generation inhibitors of SARS‐CoV‐2 RNA‐dependent RNA polymerase DOI Creative Commons
Zhonglei Wang, Liyan Yang,

Xian-qing Song

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 6, 2022

GS-441524, an RNA‐dependent RNA polymerase (RdRp) inhibitor, is a 1′-CN-substituted adenine C-nucleoside analog with broad-spectrum antiviral activity. However, the low oral bioavailability of GS‐441524 poses challenge to its anti-SARS-CoV-2 efficacy. Remdesivir, intravenously administered version (version 1.0) first FDA-approved agent for SARS-CoV-2 treatment. clinical trials have presented conflicting evidence on value remdesivir in COVID-19. Therefore, GS-441524 derivatives (VV116, ATV006, and GS-621763; 2.0, targeting highly conserved viral RdRp) could be considered as game-changers treating COVID-19 because administration has potential maximize benefits, including decreased duration reduced post-acute sequelae infection, well limited side effects such hepatic accumulation. This review summarizes current research related provides important insights into factors underlying controversial observations regarding efficacy remdesivir; overall, it offers effective launching pad developing GS-441524.

Language: Английский

Citations

48
Computational Analysis of Molnupiravir DOI Open Access

Artem V. Sharov,

Tatyana M. Burkhanova, Tuğba Taşkın‐Tok

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1508 - 1508

Published: Jan. 28, 2022

In this work, we report in-depth computational studies of three plausible tautomeric forms, generated through the migration two acidic protons N4-hydroxylcytosine fragment, molnupiravir, which is emerging as an efficient drug to treat COVID-19. The DFT calculations were performed verify structure these tautomers, well their electronic and optical properties. Molecular docking was applied examine influence structures keto-oxime, keto-hydroxylamine hydroxyl-oxime tautomers on a series SARS-CoV-2 proteins. These exhibited best affinity behavior (−9.90, −7.90, −9.30 kcal/mol, respectively) towards RdRp-RTR Nonstructural protein 3 (nsp3_range 207–379-MES).

Language: Английский

Citations

41
The impact of SARS-CoV-2 3CL protease mutations on nirmatrelvir inhibitory efficiency. Computational insights into potential resistance mechanisms DOI Creative Commons
Carlos A. Ramos‐Guzmán,

Milorad Andjelkovic,

Kirill Zinovjev

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(10), P. 2686 - 2697

Published: Jan. 1, 2023

The use of antiviral drugs can promote the appearance mutations in target protein that increase resistance virus to treatment. This is also case nirmatrelvir, a covalent inhibitor 3CL protease, or main SARS-CoV-2. In this work we show how by-residue decomposition noncovalent interactions established between drug and enzyme, combination with an analysis naturally occurring mutations, be used detect potential protease conferring nirmatrelvir. We investigate consequences these on reaction mechanism form enzyme-inhibitor complex using QM/MM methods. particular, E166V variant displays smaller binding affinity nirmatrelvir larger activation free energy for formation complex, both factors contributing observed treatment drug. conclusions derived from our anticipate introduction fitness landscape design new inhibitors adapted some possible mechanisms.

Language: Английский

Citations

23
Efficacy and Safety of Molnupiravir Treatment for COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials DOI Open Access
Fangyuan Tian,

Qiyi Feng,

Zhaoyan Chen

et al.

International Journal of Antimicrobial Agents, Journal Year: 2023, Volume and Issue: 62(2), P. 106870 - 106870

Published: May 26, 2023

Language: Английский

Citations

23
New Perspectives on Antimicrobial Agents: Molnupiravir and Nirmatrelvir/Ritonavir for Treatment of COVID-19 DOI
Robert L. Atmar, Natalie Finch

Antimicrobial Agents and Chemotherapy, Journal Year: 2022, Volume and Issue: 66(8)

Published: July 12, 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged to cause pandemic disease in the past 2 years, leading significant worldwide morbidity and mortality. At beginning of pandemic, only nonspecific treatments were available, but recently two oral antivirals have received emergency use authorization from U.S. Food Drug Administration for treatment mild moderate coronavirus (COVID-19). Molnupiravir targets viral polymerase causes lethal mutations within virus during replication. Nirmatrelvir SARS-CoV-2's main protease, it is combined with ritonavir delay its metabolism allow nirmatrelvir inhibit proteolytic cleavage polyproteins replication, preventing efficient production. Both drugs

Language: Английский

Citations

38
Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors DOI Creative Commons

Letian Song,

Shenghua Gao, Bing Ye

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(1), P. 87 - 109

Published: Aug. 9, 2023

The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role the virus life cycle. covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) non-covalent ensitrelvir have shown efficacy clinical trials been approved therapeutic use. Effective antiviral drugs are needed to fight pandemic, while inhibitors could be promising alternatives due their selectivity favorable druggability. Numerous desirable properties developed based on available crystal structures Mpro. In this article, we describe medicinal chemistry strategies applied discovery optimization inhibitors, followed by general overview critical analysis information. Prospective viewpoints insights into current development also discussed.

Language: Английский

Citations

20
Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors DOI

Aijia Wu,

Kunyu Shi,

Jiaxing Wang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 263, P. 115923 - 115923

Published: Oct. 31, 2023

Language: Английский

Citations

17
Enhanced Nasal Deposition and Anti-Coronavirus Effect of Favipiravir-Loaded Mucoadhesive Chitosan–Alginate Nanoparticles DOI Creative Commons
Khent Primo Alcantara, Nonthaneth Nalinratana, Nopporn Chutiwitoonchai

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2680 - 2680

Published: Dec. 1, 2022

Favipiravir (FVR) is a repurposed antiviral drug for treating mild to moderate cases of the novel coronavirus disease 2019 (COVID-19). However, its poor solubility and permeability limit clinical efficacy. To overcome physicochemical pharmacokinetic limitations, we statistically designed mucoadhesive chitosan–alginate nanoparticles (MCS-ALG-NPs) as new carrier FVR using response surface methodology, which provided suitable characteristics transmucosal delivery. The use polymers intranasal administration promotes residence time contact in mucus membrane. optimized FVR-MCS-ALG-NPs demonstrated superior mucoadhesion, higher permeation deposition nasal mucosa, significant increase inhibition viral replication over 35-fold compared with free FVR. overall results suggest that MCS-ALG-NPs could be used an effective enhance activity against COVID-19.

Language: Английский

Citations

27