Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 944 - 944

Published: April 10, 2023

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of has given rise to multiple variants varying pathogenicity transmissibility, such as Delta Omicron variants. Individuals advanced age or underlying comorbidities, including hypertension, diabetes cardiovascular diseases, are at higher risk increased disease severity. Hence, this resulted in an urgent need for development better therapeutic preventive approaches. This review describes origin human coronaviruses, particularly well sub-variants. Risk factors that contribute severity implications co-infections also considered. In addition, various antiviral strategies against COVID-19, novel repurposed drugs targeting viral host proteins, immunotherapeutic strategies, discussed. We critically evaluate current emerging vaccines their efficacy, immune evasion new impact on diagnostic testing examined. Collectively, global research public health authorities, along all sectors society, prepare upcoming future coronavirus outbreaks.

Language: Английский

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SARS-CoV-2 spike S2-specific neutralizing antibodies

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: May 31, 2023

Since the onset of coronavirus disease 2019 (COVID-19), numerous neutralizing antibodies (NAbs) against severe acute respiratory syndrome 2 (SARS-CoV-2) have been developed and authorized for emergency use to control pandemic. Most COVID-19 therapeutic NAbs prevent S1 subunit SARS-CoV-2 spike (S) protein from binding human host receptor. However, emergence immune escape variants, which possess frequent mutations on subunit, may render current ineffective. In contrast, relatively conserved S2 S can elicit with broader potency various variants. this review, specificity functional features targeting different domains are collectively discussed. The knowledge learned investigation S2-specific provides insights potential strategies developing antibody cocktail therapy next-generation vaccine.

Language: Английский

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Deuremidevir and Simnotrelvir–Ritonavir for the Treatment of COVID-19

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(9), P. 1306 - 1309

Published: Aug. 4, 2023

Deuremidevir hydrobromide tablets and simnotrelvir tablets/ritonavir (co-packaged) were approved by the Chinese National Medical Products Administration for treatment of mild to moderate COVID-19 in January 2023. Both formulations contain small-molecule anti-SARS-CoV-2 agents. Deuremidevir, an oral nucleoside analog, is a broad-spectrum virus replication inhibitor targeting highly conserved RNA-dependent RNA polymerase. Simnotrelvir-ritonavir co-packaged combination drug consisting ritonavir tablets. Simnotrelvir antiviral agent 3-chymotrypsin-like protease, which essential SARS-CoV-2 viral replication. Previous clinical trials revealed that both deuremidevir simnotrelvir-ritonavir effective well tolerated COVID-19.

Language: Английский

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Recent Advances on Targeting Proteases for Antiviral Development

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 366 - 366

Published: Feb. 27, 2024

Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible causing diseases humans, like West Nile virus (WNV) recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding mechanisms behind blocking protease’s function is pivotal development antiviral drugs therapeutical strategies. Apart from directly inhibiting protease, usually by targeting its active site, have been explored to impair activity, such as inducing protein aggregation, allosteric sites or degradation cellular proteasomes, which be extremely valuable when considering emerging drug-resistant strains. In this review, we aim discuss advances on a broad range inhibitors, therapies molecular approaches inactivation degradation, giving insight different possible strategies against class target.

Language: Английский

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Highlights on Fluorine-containing Drugs Approved by U.S. FDA in 2023

Current Topics in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(10), P. 843 - 849

Published: March 6, 2024

Fluorine continues to show its potential applications in drug discovery and development, as reflected by twelve drugs being fluorinated out of the fifty-five approved FDA 2023. This concise review highlights each these fluorine-containing past year, including brand name, date approval, composition, sponsors, indication, mechanism action. The relevant future trend is also briefly discussed.

Language: Английский

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A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID‐19 patients

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(3)

Published: March 1, 2024

Abstract The bacteriophage behavior of SARS‐CoV‐2 during the acute and post‐COVID‐19 phases appears to be an important factor in development disease. early use antibiotics seems crucial inhibit disease progression—to prevent viral replication gut microbiome, control toxicological production from human microbiome. To study impact specific on recovery COVID‐19 long COVID (LC) taking into account: vaccination status, comorbidities, wave, time initiation antibiotic therapy concomitant corticosteroids nonsteroidal anti‐inflammatory drugs (NSAIDs). A total 211 patients were included study: which 59 vaccinated with mRNA vaccines against while 152 unvaccinated. Patients enrolled three waves: September 2020 October 2022, corresponding emergence pre‐Delta, Delta, Omicron variants virus. criteria for enrolling were: oropharyngeal swab positivity or fecal findings; moderate symptoms intake; measurement blood oxygen saturation period illness. combinations, such as amoxicillin clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 tablets h), first choice, suggested previous data, azithromycin (500 24 above, allows healthcare professionals focus microbiome its implications patient care. primary outcome measured this was estimated average treatment effect, quantified difference mean between receiving those not at 3 9 days after start treatment. In analysis, both unvaccinated groups had a median illness duration 7 (interquartile range [IQR] 6–9 each; crude hazard ratio [HR] = 0.94, p 0.700). pre‐Delta Delta waves 8 (IQR 7–10 days), it shorter, 6.5 days, 6–8 days; HR 1.71, < 0.001). These results confirmed by multivariate analysis. comorbidities significantly longer duration: days) compared without (crude 0.75, 0.038), but result analysis statistical significance lost. Early resulted shorter 4.74, Concomitant NSAIDs did reduce prolonged ( 0.041). subgroup 42 3–6 (median IQR 8–10 others 0.542, 0.001), also adjusted HR. study, statistically significant reduction observed among who received played role maintaining higher levels saturation. addition, is worth noting that number phase develop LC.

Language: Английский

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Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 22, 2023

Abstract Objective To compare the effectiveness of Paxlovid vs. sotrovimab and molnupiravir in preventing severe COVID-19 outcomes non-hospitalised high-risk adult patients. Design With approval NHS England, we conducted a real-world cohort study using OpenSAFELY-TPP platform. Setting Patient-level electronic health record data were obtained from 24 million people registered with general practice England that uses TPP software. The primary care securely linked on infection therapeutics, hospital admission, death within platform, covering period where both first-line treatment options community settings. Participants Non-hospitalised patients at high risk treated Paxlovid, or between February 11, 2022 October 1, 2022. Interventions administered by Medicine Delivery Units. Main outcome measure related hospitalisation 28 days after initiation. Results A total 7683 eligible (n=4836) (n=2847) included main analysis. mean age was 54.3 (SD=14.9) years; 64% female, 93% White had three more vaccinations. Within initiation, 52 (0.68%) hospitalisations/deaths observed (33 19 (0.67%) sotrovimab). Cox proportional hazards model stratified region showed adjusting for demographics, categories, vaccination status, calendar time, body mass index other comorbidities, associated similar event as (HR=1.14, 95% CI: 0.62 to 2.08; P=0.673). propensity score weighted also comparable risks these two groups (HR=0.88, 0.45 1.71; P=0.700). An exploratory analysis comparing users 802 (11 (1.37%) hospitalisations/deaths) some evidence favour but variation effect estimates models (HR ranging 0.26 0.61). Conclusion In routine no substantial difference those who received 2022, when different subvariants Omicron dominant.

Language: Английский

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Toward the Design of Allosteric Effectors: Gaining Comprehensive Control of Drug Properties and Actions

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

While the therapeutic potential of allosteric drugs is increasingly realized, discovery effectors largely incidental. The rational design requires new state-of-the-art approaches to account for distinct characteristics ligands and their modes action. We present a broadly applicable computational framework obtaining site-effector pairs, providing targeted, highly specific, tunable regulation any functional site. validated using main protease from SARS-CoV-2 K-Ras

Language: Английский

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Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform

The Lancet Regional Health - Europe, Journal Year: 2023, Volume and Issue: 34, P. 100741 - 100741

Published: Oct. 9, 2023

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed compare nirmatrelvir/ritonavir versus sotrovimab and molnupiravir preventing severe outcomes non-hospitalised high-risk adult patients during Omicron waves. With approval NHS England, we conducted a cohort using OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people England securely linked with on infection therapeutics, hospital admission, death, covering period where both first-line treatment options community (February 10, 2022–November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator nirmatrelvir/ritonavir, which antivirals. Cox proportional hazards model stratified by area risk 28-day related hospitalisation/death across groups. A total 9026 eligible treated (n = 5704) 3322) included main analysis. The mean age 52.7 (SD 14.9) years 93% (8436/9026) had three or more vaccinations. Within 28 days after initiation, 55/9026 (0.61%) hospitalisations/deaths observed (34/5704 [0.60%] 21/3322 [0.63%] sotrovimab). After adjusting for demographics, categories, vaccination status, calendar time, body mass index other comorbidities, no significant difference outcome users (HR 0.89, 95% CI: 0.48–1.63; P 0.698). Results propensity score weighted also showed non-significant groups 0.82, 0.45–1.52; 0.535). analysis comparing 1041 (13/1041 [1.25%] hospitalisations/deaths) association favour 0.45, 0.22–0.94; 0.033). In routine substantial those who received February November 2022, when subvariants BA.2, BA.5, BQ.1 dominant. UK Research Innovation, Wellcome Trust, Medical Council, National Institute Health Care Research, Data UK.

Language: Английский

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The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 976 - 976

Published: April 16, 2023

Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced risk severe clinical progress COVID-19. However, breakthrough infections has increased, early administration an effective antiviral treatment is significant in order to prevent progression COVID-19 vulnerable patients with comorbidities.Adults confirmed infection were included a matched-pair retrospective study based on age, gender, comorbidities vaccination status. They divided into two groups: group A (n = 200) consisted outpatients at increased who treated nirmatrelvir/ritonavir B non-hospitalized did not receive treatment. Demographic data, outcome (death, intubation), days hospitalization, time for recovery, adverse events compliance reported.The median age (75.24 ± 13.12 years 76.91 14.02 comparison group) proportion males (59% vs. 60.5%, respectively) similar between groups. total 6.5% 10.5% unvaccinated SARS-CoV-2. Three from (1.5%) one hundred eleven (55.5%) required hospitalization. The duration hospitalization (3 10 B, p < 0.001) needed recovery (5 9 days, was shorter group. rebound within 8-12 after diagnosis documented 8% B.Oral high-risk safe preventing pneumonia. Early agents combined full scheme avoid outcomes.

Language: Английский

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