Variant-Specific Viral Kinetics in Acute COVID-19 DOI Open Access
Ruy M. Ribeiro, Manish C. Choudhary,

Rinki Deo

и другие.

The Journal of Infectious Diseases, Год журнала: 2023, Номер 228(Supplement_2), С. S136 - S143

Опубликована: Авг. 31, 2023

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain transmission efficiency and provide insights on pathogenesis prevention. We evaluated SARS-CoV-2 from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to highest maximum load shortest time symptom onset peak. There were no significant clearance variants. Viral decline was biphasic with first- second-phase decays having half-lives 11 hours 2.5 days, respectively, among variants, especially second phase. These results suggest that while exist, post-peak all appeared be efficiently cleared by host. Clinical Trials Registration. NCT04518410.

Язык: Английский

SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy DOI Creative Commons

Gregory E. Edelstein,

Julie Boucau, Rockib Uddin

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 27, 2023

To compare the frequency of replication-competent virologic rebound with and without nirmatrelvir-ritonavir treatment for acute COVID-19. Secondary aims were to estimate validity symptoms detect incidence emergent nirmatrelvir-resistance mutations after rebound.

Язык: Английский

Процитировано

5

COVID-19 Therapeutics for Nonhospitalized Patients—Updates and Future Directions DOI Open Access
Kara W. Chew, Preeti Malani, Rajesh T. Gandhi

и другие.

JAMA, Год журнала: 2023, Номер 330(16), С. 1519 - 1519

Опубликована: Сен. 29, 2023

In this Viewpoint, the authors summarize therapeutic landscape for COVID-19, discuss who is most likely to benefit from treatment, provide an update on managing illness in immunocompromised individuals, and highlight how improve COVID-19 treatment.

Язык: Английский

Процитировано

5

Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance DOI Creative Commons
Tin Phan, Ruy M. Ribeiro,

Gregory E. Edelstein

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

Abstract In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation nirmatrelvir-ritonavir near time symptom onset, coupled incomplete clearance, appear be main factors leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance Finally, our demonstrates that extending course treatment, in particular 10-day regimen, may greatly diminish risk for people mild-to-moderate COVID-19 and who at high severe disease. Altogether, results suggest some individuals, standard 5-day starting around onset completely eliminate virus. Thus, after ends, can if an effective adaptive has fully developed. These findings on role target preservation clearance also offer possible explanation other SARS-CoV-2. Importance Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Язык: Английский

Процитировано

1

<i>In Vitro</i> Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2 DOI Creative Commons
A. N. Narovlyansky, М. В. Филимонова,

N. G. Tsyshkova

и другие.

Acta Naturae, Год журнала: 2024, Номер 15(4), С. 83 - 91

Опубликована: Янв. 17, 2024

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid foundation for a fundamental analysis of this viral family, as well search effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, screening low-molecular-weight drug candidates outpatient medicine continues. opportunities ways accelerate development antiviral drugs other pathogens are being discussed in context preparing next pandemic. In 2012–2015, Tsyshkova et al. synthesized group water-soluble compounds exhibiting an activity, whose chemical structure was similar that arbidol. Among those, there were number based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member rather extensive compounds, dihydrochloride 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited reliable effect SARS-CoV-2 vitro. At concentration 52.0 μM, compound completely inhibited replication virus with infectious activity 106 TCID50/mL. curves analyzed indicate specificity its action. Interferon-inducing suppression syncytium formation induced spike protein (S-glycoprotein) 89%, also revealed. view synthetic accessibility − high (IC50 = 1.06 µg/mL) selectivity index (SI 78.6) appears meets requirements COVID-19 prevention treatment.

Язык: Английский

Процитировано

1

Variant-Specific Viral Kinetics in Acute COVID-19 DOI Open Access
Ruy M. Ribeiro, Manish C. Choudhary,

Rinki Deo

и другие.

The Journal of Infectious Diseases, Год журнала: 2023, Номер 228(Supplement_2), С. S136 - S143

Опубликована: Авг. 31, 2023

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain transmission efficiency and provide insights on pathogenesis prevention. We evaluated SARS-CoV-2 from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to highest maximum load shortest time symptom onset peak. There were no significant clearance variants. Viral decline was biphasic with first- second-phase decays having half-lives 11 hours 2.5 days, respectively, among variants, especially second phase. These results suggest that while exist, post-peak all appeared be efficiently cleared by host. Clinical Trials Registration. NCT04518410.

Язык: Английский

Процитировано

3