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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
The dosage favipinavir accepted in China is one day loading dose of 32,000 mg daily in two 1,600 mg doses followed by 1,200 mg for 2–14 days [27]. In another prospective and randomized study with 120 patients showing moderate to severe COVID-19 symptoms was compared with Arbidol. Differences in recovery rate was observed on day 7 in patients with moderate symptoms, while no significant change was observed in patients with severe symptoms [28].
Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Arbidol is an antiviral agent used to treat Zika virus. The viral infection during pregnancy is known to cause multiple congenital anomalies of the central nervous system. In two studies of pregnant rats given the drug at several times the human therapeutic dose, and no birth defects were observed. However, animal models are poor predictors of human teratogenicity.
Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Shailendra Dwivedi, Aakanksha Rawat, Amit Ranjan, Ruchika Agrawal, Radhieka Misra, Sunil Kumar Gupta, Surekha Kishore, Sanjeev Misra
A prospective, randomized, controlled, open-label multi-center trial compared the efficacy of umifenovir (Arbidol) to favipiravir among 240 (120 each drug) adult confirmed COVID-19 patients. Each patient received either umifenovir (Arbidol) as 200 mg thrice daily or favipiravir 1,600 mg twice daily on the first day followed by 600 mg twice daily for 10 days. On day 7 of follow-up, the clinical recovery rate did not differ significantly between the favipiravir group (61.2%) and the Arbidol group (51.6%). Favipiravir was associated with shorter latencies for recovery from fever (difference: 1.70 days, P < 0.0001) and cough (difference: 1.75 days, P < 0.0001). Rise in the level of serum uric acid was also reported in the favipiravir group. Otherwise, both drugs were found to be similarly effective so far and a clinical decision needs to be made based on the disease status and comorbidity of the patient [7] [REF: use original ref, not review].
Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability
Published in Expert Review of Anti-infective Therapy, 2022
Sujit Kumar Debnath, Monalisha Debnath, Rohit Srivastava, Abdelwahab Omri
Furin-like cleavage sites are present in the spike protein of SARS-CoV-2. Azithromycin (macrolide antibiotic) effectively minimized the level of furin enzyme by interfering with intracellular replication by endosome recycling and increasing the Golgi network pH resulting in the diminished activity of the virus [44]. That’s why azithromycin has been recommended in COVID-19 treatment. After binding with the DC-SIGN receptor, a pH-dependent entry into target cells was observed in SARS-CoV-1. Endosomes are activated in an acidic pH, resulting in the fusion of viral endosomal and membranes and releasing the viral SARS-CoV-1 genome into the cytosol. Chloroquine possesses an inhibitory role in COVID-19 by elevating endosomal pH, preventing endocytosis, and destroying virus-endosome fusion [45]. This activity made sense to explore the possible effect of chloroquine and hydroxychloroquine against SARS-CoV-2. Arbidol is an anti-influenza drug that neutralizes SARS-CoV-2 and is superior to lopinavir-ritonavir in COVID-19 treatment. The detailed mechanism of inhibition is not revealed yet. It is a broad-spectrum antiviral drug that prevents viral lipid capsule contact, adhesion, and fusion with the host cell membrane [46]. Molecular dynamics simulation-based analyses revealed that arbidol binds with a higher affinity with receptor-binding domain (RBD)/ ACE2. After tying with viral glycoprotein, this drug restricted the conformational rearrangements associated with viral entry and membrane fusion [47].
Interferon-α2b induced anemia in severe coronavirus disease 2019 patients: a single centered, retrospective study
Published in Immunopharmacology and Immunotoxicology, 2021
Xina Li, Tong Liu, Xin Hai, Le Li
In our study, nebulized IFN-α2b was administrated in all patients as a basic antiviral regimen and arbidol was the following one. In a recent study, Li et al. found arbidol accelerates and enhances the process of viral clearance, particularly in mild illnesses. The side effects of arbidol include nausea, diarrhea, dizziness, and elevated serum transaminase in COVID-19 treatment [31]. Abidol is considered to be safe and has little impact on Hb level [32]. Therefore, we speculated that the Hb reduction was not induced by abidol. It is well known that ribavirin, a guanosine nucleoside analog, is associated with hemolysis. Ribavirin depletes the adenosine triphosphate level within red blood cells and induces defective antioxidant defense, which resulting in dose-dependent hemolytic anemia. Hemolysis has been noted in evaluating the effect of ribavirin in the treatment of severe acute respiratory syndrome (SARS) coronavirus infection [33,34]. Of note, ribavirin was used in less than half (42.0%) of Hb reduction patients. The duration of ribavirin was nearly 3.4 days. The Hb level declines on days 8 to 10 and recovers to nadir approximately 4 weeks later [35,36]. The short duration use of ribavirin was unreliable to explain the reason for the Hb level decrease. Moreover, the IFN-α2b and ribavirin were declined in the IFN-stop group, and the Hb value was recovered 7 days later. In addition, the Hb value had no change when ribavirin was declined in the non-IFN-stop group (Figure 2C). These illustrated that nebulized IFN-α2b may be the only possible cause of Hb reduction.
Recent progress in the repurposing of drugs/molecules for the management of COVID-19
Published in Expert Review of Anti-infective Therapy, 2021
Divakar Sharma, Adinarayana Kunamneni
FDA approved nucleotide inhibitors (Sofosbuvir, Ribavirin, and Remdesivir) interfere with the synthesis of viral mRNA targeting RdRp of Hepatitis C Virus (HCV), Dengue virus, Ebola, Marburg virus and Zika virus. These drugs also exhibited the potential activity against the SARS-CoV-2 in-vitro [11–13], and could be repurposed for the treatment of COVID-19. Till June 2020, Favipiravir/Favilavir has been approved in Japan, China, Italy, Russia and India but in the USA it is still not approved (Its completed phase III trials). These countries have been started clinical trials for the treatment of COVID-19 [14]. In a randomized clinical trial in China, the researchers reported a 71.43% recovery rate within 7 days in the group of COVID-19 patients treated by favipiravir and 55.86% recovery rate in the arbidol group [15]. Arbidol is an antiviral drug (Russian made) used for the treatment of influenza diseases in Russia and China. Therefore, this trial suggested the favipiravir should be preferred over the arbidol for the treatment of COVID-19. Galidesivir (nucleoside analog) is an antiviral drug used for the treatment of HCV, Zika, and Ebola virus [16]. These nucleotide and nucleoside analogs could be repurposed for the treatment of COVID-19 outbreak.