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Therapeutic Challenges in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Alaa A. A. Aljabali, Murtaza M. Tambuwala, Debmalya Barh, Kenneth Lundstrom
RNA-dependent RNA polymerase (RdRp) inhibitors have previously shown efficacy against different viruses such as influenza virus, hepatitis C virus (HCV), and Zika virus (ZIKV), and are therefore potential targets as antiviral drugs against COVID-19 [9]. Molecular docking studies showed high binding affinity of remdesivir (RDV) [15], ribavirin (RBV), favipiravir (FPV), sofosbuvir, galidesivir, and tenofovir to SARS-CoV-2, indicating their potency as antiviral drugs for COVID-19 patients [10]. Moreover, RDV has demonstrated antiviral activity in human cell lines and primary cell lines against HCoV-229E, HCoV-OC43, SARS-CoV, and MERS-CoV [11] and reduction in SARS-CoV and MERS-CoV viral loads in mice and rhesus macaques, respectively [12]. RDV has been evaluated for safety and efficacy in a randomized, placebo-controlled clinical trial in 1,062 COVID-19 patients [13]. Intravenous administration of RDV significantly reduced the recovery time from 15 to 10 days in hospitalized patients. However, interim results from the WHO Solidarity Trial indicated that RDV, HCQ, lopinavir (LPV), and interferon regimens had minor or no effect on hospitalized COVID-19 patients based on overall mortality, the start of ventilation, and length of hospital stay [14]. In clinical evaluations, it was demonstrated that RDV was associated with significantly enhanced recovery, with a 62% reduced odds of death compared to standard care [4].
Cytokine storm associated coagulation complications in COVID-19 patients: Pathogenesis and Management
Published in Expert Review of Anti-infective Therapy, 2021
Shreya R. Savla, Kedar S. Prabhavalkar, Lokesh K. Bhatt
The first-line treatment options for COVID-19 are the classic antiviral drugs, which are important in reducing mortality in mild to severe cases along with simultaneous organ function support [158]. The antiviral drugs used in SARS-CoV-2 infection include Remdesivir, Ribavarin, Galidesivir, Tenofovir, Lopinavir, Ritonavir and Sofosbuvir [158]. There have been previous reports of the anti-inflammatory properties of these antiviral drugs, when used individually or in combination as highly active antiviral therapies [159]. The anti-malarial drugs like chloroquine and hydroxychloroquine have also shown beneficial effects against SARS-CoV-2 infection. Hydroxychloroquine was found to possess immunomodulatory effects, which have been useful in targeting the cytokine storm in moderate to severe cases [37,160]. Additionally, these antiviral medications have been effectively combined with several biological agents targeting specific cytokines, like IL-6 R monoclonal antibodies, IL-1 inhibitors, TNF inhibitors, JAK inhibitors, etc. Tocilizumab has also effectively reduced microthrombosis. Adopting drugs or compounds that work against a specific cytokine is associated with the risk of targeting only a specific part of the cytokine storm. Furthermore, immunosuppressive medication should be used rationally as it may result in a compromise of host innate immunity [159].
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.
Zika virus pathogenesis and current therapeutic advances
Published in Pathogens and Global Health, 2021
Caroline Mwaliko, Raphael Nyaruaba, Lu Zhao, Evans Atoni, Samuel Karungu, Matilu Mwau, Dimitri Lavillette, Han Xia, Zhiming Yuan
Currently, a few drugs, including Pinocembrin and BCX4430, also known as Galidesivir, have completed phase 1 clinical trials performed by Biocryst Pharmaceuticals. Galidesivir was administered intravenously in 24 healthy volunteers. In trials, this drug was shown to be safe and tolerable. Intramuscular administration and animal models have also been used to show that this drug has survival benefits against several pathogens, including Ebola [129], Marburg, YFV, WNV [127] and ZIKV [129]. Additionally, Galidesivir has shown broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, and flaviviruses [151]. Nevertheless, this drug has been shown to confer resistance as a result of an E460D substitution in the NS5 protein of TBEV [128], which represents a major challenge in the development of viral replication inhibitors since the viruses are rapidly evolving.