The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(6), С. 1297 - 1298
Опубликована: Июль 8, 2024
Язык: Английский
Viruses, Год журнала: 2023, Номер 15(11), С. 2151 - 2151
Опубликована: Окт. 25, 2023
Molnupiravir, a prodrug known for its broad antiviral activity, has demonstrated efficacy in animal models of COVID-19, prompting clinical trials, which initial results indicated significant effect against the disease. However, subsequent studies did not confirm these findings, leading to refusal molnupiravir permanent market authorization many countries. This report critically assessed 22 published 18 reports that investigated with purpose determining how well design informed human studies. We found administered doses most involving COVID-19 were disproportionately higher than dose recommended use. Specifically, when adjusted body surface area, over half used exceeded twice dose. Direct comparison reported drug exposure across species after oral administration use was underestimated some and overestimated others. Frequently, given prophylactically or shortly SARS-CoV-2 inoculation models, contrast trials where such timing is consistently achieved. Furthermore, five-day treatment duration humans several Collectively, we suggest elements under examination contributed preference favoring molnupiravir, thus inflated expectations COVID-19. Addressing may offer strategies enhance Such include increment, early initiation, by inhalation, combination therapy.
Язык: Английский
Процитировано
3
Research Square (Research Square), Год журнала: 2023, Номер unknown
Опубликована: Авг. 18, 2023
Abstract Purpose Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended the international guidelines, does not prevent this certainty. Dual therapies might therefore act synergistically. Methods This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) combinations nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ mABs during Omicron surge. Co-primary endpoints were prolonged viral (≥10 6 copies/ml at day 21 after initiation) and days SARS-CoV-2 load ≥10 copies/ml. Therapeutic risk groups by odds ratios Fisher’s tests Kaplan-Meier analysis long-rank tests. Multivariable regression was performed. Results 144 patients included a median time 8.0 (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p=0.03) initiations later than five diagnosis (p<0.01) significantly associated longer shedding. Viral 14.6% (n=21/144), especially underlying HM (OR 3.5; 95% CI 1.2-9.9; p=0.02). Clinical courses COVID-19 mild to moderate only few adverse effects potentially contributed combination treatment. Conclusion effectively prevented 85.6% cases. Considering rapid clearance rates low toxicity, individualized dual therapeutic approaches may thus be advantageous high-risk patients.
Язык: Английский
Процитировано
2
Опубликована: Ноя. 6, 2023
Current small molecule-based treatments for pre-exposure prophylaxis or active infection of SARS-CoV-2 remain poorly available worldwide and risk-inducing drug-induced viral resistance. Compounds that block multiple aspects the replication cycle would be expected to pose a higher genetic barrier drug Therefore, marine algae extract library, two distinct biochemical assays were used screen natural products could inhibit well-defined validated COVID-19 targets, disruption Spike protein/ACE-2 interaction main protease (Mpro) SARS-CoV-2. Upon initial screening 86 crude extracts, we counter-screened performed an untargeted metabolomic analysis 16 cyanobacterial extracts. This orthogonal approach revealed three extracts with similar biological profiles, all from collection sites, leading isolation unusual saturated fatty acid, jobosnoic acid (1). We confirmed 1 demonstrated dual inhibitory activity towards both targets while retaining against Spike-RBD/ACE-2 omicron variant. To initially explore its Structure Activity Relationship (SAR), semi-synthetically accessed methyl benzyl ester derivatives 1, which acute loss bioactivity in assays. effort has provided copious amounts product warrants further investigation terms SAR, determination absolute configuration C2 C5 substituents understanding specific mechanisms action binding site potentially describe new therapeutic avenues development.
Язык: Английский
Процитировано
1
iLABMED, Год журнала: 2024, Номер 2(2), С. 88 - 97
Опубликована: Апрель 22, 2024
Abstract Background This study assessed the safety and efficacy of nirmatrelvir‐ritonavir (Paxlovid®) azvudine when administered sequentially or concomitantly in patients with coronavirus 2019 (COVID‐19) caused by Omicron variant. Methods Ninety‐three confirmed to be infected variant nucleic acid detection were retrospectively investigated. Information was collected on general health status, medication, adverse drug reactions (ADRs) according whether concomitantly. Data times onset, clinical manifestations, outcomes ADRs conversion a negative test also recorded. Results Possible recorded 41 (44.1%). There 22 gastrointestinal 18 hematological abnormalities 16 after sequential concomitant treatment azvudine. Liver enzyme levels increased nine cases creatinine clearance decreased two. Cases atrial fibrillation ( n = 1), sleep disorder 2), rash dizziness weakness 5) documented. Only vomiting, poor appetite, diarrhea, xerostomia, bitter taste, considered probable ADRs; others thought possible ADRs. In all cases, did not turn first antiviral applied. The 28 before discharge. remaining 65 (69.9%) returned receiving second agent. Conclusions Treatment is safe effective COVID‐19
Язык: Английский
Процитировано
0
The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(6), С. 1297 - 1298
Опубликована: Июль 8, 2024
Язык: Английский
Процитировано
0