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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
Nucleoside analogs are a class of antiviral drugs that proves to be effective against different viruses such as hepatitis B, C, and HIV. Nucleoside analogs are further classified into three classes: Mutagenic Nucleosides: This targets the viral dependence on RdRp that cause the replication of RNA from RNA template like ribavirin.Obligate Chain Terminators: This targets additional DNA synthesis and incorporation as it lacks the reactive 3′-hydroxyl group needed for this process like azidothymidine (AZT).Delayed Chain Terminators: This targets the process of transcription like Remdesivir.
Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Ganciclovir is a nucleoside analog similar to acyclovir. It has been shown readily to cross the human placenta (Gilstrap et al., 1994; Henderson et al., 1993). Ganciclovir is more toxic than acyclovir, and there is no information regarding its use during pregnancy.
The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Despite the difficulty of the problem some effective antiviral drugs have been developed against herpesviruses and retroviruses. The nucleoside analogue acycloguanosine (Acyclovir) is activated by phosphorylation via thymidine kinase, a herpesvirus encoded enzyme. The phosphorylated analogue acts then to inhibit the activity of the virus-encoded polymerase. Nucleoside and nonnucleoside inhibitors have been developed against retroviral infections as a result of the massive efforts developed in response to the AIDS epidemic (see below). Nucleoside analogues such as azidothymidine (AZT) selectively inhibit reverse transcriptase (RT) and thereby inhibit the replication of the retroviruses including HIV. A variety of nucleoside analogs have been produced to combat HIV infections (e.g., ddl, didanosine). The need for additional antiviral drugs against HIV has been driven, in part, by the ability of retroviruses like HIV to mutate and become resistant to the effects of drugs that have been developed. The introduction of protease inhibitors like nelfinavir has provided additional types of drugs active against HIV infection. These drugs in combination with RT inhibitors have provided new hope in the battle against AIDS. However, before long-term success against HIV is achieved elimination of sites of latent virus production and continued development of drugs against resistant strains will be required.
The preclinical discovery and development of molnupiravir for the treatment of SARS-CoV-2 (COVID-19)
Published in Expert Opinion on Drug Discovery, 2022
Pasquale Pagliano, Carmine Sellitto, Tiziana Ascione, Giuliana Scarpati, Veronica Folliero, Ornella Piazza, Gianluigi Franci, Amelia Filippelli, Valeria Conti
Many nucleoside analogues have been used in the treatment of viral diseases, some of these have historical value only, but other retain their antiviral efficacy years after their introduction. Antiviral activity of nucleoside analog is driven by the interaction with viral DNA/RNA polymerase or reverse transcriptase, which finally inhibits nucleic acid elongation or causes loss of viral information [19]. Active triphosphate nucleosides have poor chemical stability and cannot cross cellular barrier and penetrate the cell due to their negative charge. Drugs interacting with RdRp must be administered as nucleosides and converted into their triphosphate form, which is finally incorporated into the growing RNA chain. As conversion of a nucleoside to its monophosphate form can be a limiting passage, stable protected monophosphate nucleosides have been developed. RDV, Sofosbuvir, and Tenofovir, well-known drugs currently administered to patients with COVID-19, HCV, or HIV infection, are available as the prodrugs of their monophosphate (ProTide), which can be finally converted into the active compound once they reach the targeted cell [20,21].
Therapeutic targets for enterovirus infections
Published in Expert Opinion on Therapeutic Targets, 2020
Mira Laajala, Dhanik Reshamwala, Varpu Marjomäki
In addition to nucleoside analogs, also non-nucleoside analogs have been studied as 3Dpol inhibitors. Amiloride was shown to inhibit the infection of CVB3 and resistant mutations were identified in 3Dpol [75]. Later, the mechanism was described in more detail as amiloride was shown to increase the error rate of 3Dpol and compete with incoming nucleoside triphosphates and Mg2+ [76]. Also, other non-nucleoside analogs have been identified although the mechanism of action has not been as thoroughly shown. GPC-N114 was shown to prevent the infection of multiple enteroviruses by interfering with productive binding of the template-primer to 3Dpol by binding at the template-binding site [77]. In addition, gliotoxin and aurintricarboxlic acid inhibited the 3Dpol activity of poliovirus and EV-A71, respectively [78,79]. Furthermore, Dtrip-22 was shown to inhibit the infection of many enteroviruses by preventing the elongation action of 3Dpol [80]. BPR-3P0128 also inhibited the elongation activity of EV-A71 3Dpol but also prevented the VPg uridylylation [81].
Treatments in the COVID-19 pandemic: an update on clinical trials
Published in Expert Opinion on Emerging Drugs, 2020
Yanyi Tao, Liang V. Tang, Yu Hu
COVID-19 belongs to the same genus of CoV as SARS-COV and MERS-COV, both of which are beta-cov. Whole genome sequencing showed that COVID-19 shared 79.5% of sequence identity with SARS-CoV [5]. In combination with the treatment experience of SARS-COV and MERS-COV, several potential drugs have been proposed for treatment of SARS-CoV-2, including arbidol, chloroquine, and human immunodeficiency virus-1 (HIV-1) protease inhibitors (lopinavir/ritonavir), new nucleoside analogues (remdesivir, GS-5734) and convalescent plasma. As for clinical broad-spectrum antiviral drugs, neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, etc.) are not recommended for clinical use, since the coronavirus does not produce neuraminidase. In addition, nucleoside analogues are not recommended neither due to their little efficacy in vitro experiments or existing clinical studies. However, nucleoside analogues can be used in combination with interferon for antiviral treatment [6,7].