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1.
Eur J Med Chem ; 231: 114136, 2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1778107

ABSTRACT

Nucleosides and their derivatives are a well-known and well-described class of compounds with antiviral activity. Currently, in the era of the COVID-19 pandemic, scientists are also looking for compounds not related to nucleosides with antiviral properties. This review aims to provide an overview of selected synthetic antiviral agents not associated to nucleosides developed against human viruses and introduced to preclinical and clinical trials as well as drugs approved for antiviral therapy over the last 10 years. The article describes for the first time the wide classification of such antiviral drugs and drug candidates and briefly summarizes the biological target and clinical applications of the compounds. The described compounds are arranged according to the antiviral mechanism of action. Knowledge of the drug's activity toward specific molecular targets may be the key to researching new antiviral compounds and repositioning drugs already approved for clinical use. The paper also briefly discusses the future directions of antiviral therapy. The described examples of antiviral compounds can be helpful for further drug development.


Subject(s)
COVID-19 , Nucleosides , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Nucleosides/pharmacology , Nucleosides/therapeutic use , Pandemics , SARS-CoV-2
2.
Signal Transduct Target Ther ; 7(1): 26, 2022 01 27.
Article in English | MEDLINE | ID: covidwho-1655545

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Design/trends , Drug Repositioning , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/chemistry , Adrenal Cortex Hormones/therapeutic use , Antibodies, Viral/chemistry , Antibodies, Viral/therapeutic use , Antiviral Agents/chemistry , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/therapeutic use , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Humans , Models, Molecular , Nucleosides/chemistry , Nucleosides/therapeutic use , Protein Conformation , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , Virus Internalization/drug effects , Virus Release/drug effects , Virus Replication/drug effects
3.
Environ Mol Mutagen ; 63(1): 37-63, 2022 01.
Article in English | MEDLINE | ID: covidwho-1620131

ABSTRACT

This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, ß-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , Cytidine/analogs & derivatives , DNA Damage/drug effects , Hydroxylamines/adverse effects , Nucleosides/adverse effects , SARS-CoV-2/genetics , Amides/adverse effects , Amides/therapeutic use , Antiviral Agents/therapeutic use , Cytidine/adverse effects , Cytidine/therapeutic use , Deoxyuridine/adverse effects , Deoxyuridine/analogs & derivatives , Deoxyuridine/therapeutic use , Genome, Human/drug effects , Humans , Hydroxylamines/therapeutic use , Mutagenesis/drug effects , Nucleosides/therapeutic use , Pyrazines/adverse effects , Pyrazines/therapeutic use , Ribavirin/adverse effects , Ribavirin/therapeutic use , SARS-CoV-2/drug effects
4.
Microbiol Spectr ; 9(3): e0153721, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1532984

ABSTRACT

The necessity for intravenous administration of remdesivir confines its utility for treatment of coronavirus disease 2019 (COVID-19) to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524), against viruses that cause diseases of human public health concern, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had activity nearly equivalent to that of remdesivir in primary-like human small airway epithelial cells. Our results warrant in vivo efficacy evaluation of ODBG-P-RVn. IMPORTANCE While remdesivir remains one of the few drugs approved by the FDA to treat coronavirus disease 2019 (COVID-19), its intravenous route of administration limits its use to hospital settings. Optimizing the stability and absorption of remdesivir may lead to a more accessible and clinically potent therapeutic. Here, we describe an orally available lipid-modified version of remdesivir with activity nearly equivalent to that of remdesivir against emerging viruses that cause significant disease, including Ebola and Nipah viruses. Our work highlights the importance of such modifications to optimize drug delivery to relevant and appropriate human tissues that are most affected by such diseases.


Subject(s)
Adenosine Monophosphate/therapeutic use , Adenosine/therapeutic use , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Nucleosides/therapeutic use , Prodrugs/therapeutic use , Adenosine/analogs & derivatives , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Glyceryl Ethers/therapeutic use , Humans , Lipids , SARS-CoV-2
5.
Curr Top Med Chem ; 21(32): 2909-2927, 2021.
Article in English | MEDLINE | ID: covidwho-1332065

ABSTRACT

Synthetic nucleoside or nucleotide analogues played a key role to the development of antiviral agents in past decades. However, low membrane permeability and insufficient cellular phosphorylation impaired the biological activity of polar nucleoside drugs because they have to penetrate the cell membrane and be phosphorylated to active metabolite stepwise by intracellular enzymes. To overcome these limitations, diverse lipophilic prodrug modifications based on nucleoside mono-, di-, and triphosphate were designed and put into practice to efficiently deliver nucleoside into the target site, and bypass the rate-limited phosphorylation step. As the most successful prodrug strategy, ProTide technology has led to the discovery of three FDA-approved antiviral agents, including sofosbuvir, tenofovir alafenadmide, and remdesivir, which has been authorized for emergency use in patients of COVID-19 in the US. In recent years, nucleoside di- and triphosphate prodrugs have also made the significant progress. This review will focus on the summary of design approach and metabolic activation path of different nucleotide prodrug strategies. The potential application of nucleotide prodrugs for the treatment of COVID-19 was also described due to the pandemic of SARS-CoV-2.


Subject(s)
Antiviral Agents , Drug Design , Nucleosides , Nucleotides , Prodrugs , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Nucleosides/pharmacology , Nucleosides/therapeutic use , Nucleotides/pharmacology , Nucleotides/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , SARS-CoV-2/drug effects
6.
J Med Virol ; 93(1): 300-310, 2021 01.
Article in English | MEDLINE | ID: covidwho-1206791

ABSTRACT

The global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), named coronavirus disease 2019, has infected more than 8.9 million people worldwide. This calls for urgent effective therapeutic measures. RNA-dependent RNA polymerase (RdRp) activity in viral transcription and replication has been recognized as an attractive target to design novel antiviral strategies. Although SARS-CoV-2 shares less genetic similarity with SARS-CoV (~79%) and Middle East respiratory syndrome coronavirus (~50%), the respective RdRps of the three coronaviruses are highly conserved, suggesting that RdRp is a good broad-spectrum antiviral target for coronaviruses. In this review, we discuss the antiviral potential of RdRp inhibitors (mainly nucleoside analogs) with an aim to provide a comprehensive account of drug discovery on SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Enzyme Inhibitors/therapeutic use , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Enzyme Inhibitors/pharmacology , Nucleosides/pharmacology , Nucleosides/therapeutic use , RNA-Dependent RNA Polymerase/genetics , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/metabolism
7.
Eur Rev Med Pharmacol Sci ; 25(5): 2435-2448, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1145761

ABSTRACT

OBJECTIVE: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). MATERIALS AND METHODS: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. RESULTS: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Therapy, Combination/methods , Nucleosides/therapeutic use , Protease Inhibitors/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Atazanavir Sulfate , Darunavir , Drug Combinations , Early Medical Intervention , Emtricitabine , Humans , Lamivudine , Lopinavir , Molecular Docking Simulation , Ritonavir , SARS-CoV-2
8.
Molecules ; 26(4)2021 Feb 13.
Article in English | MEDLINE | ID: covidwho-1085052

ABSTRACT

Coronaviruses (CoVs) are positive-sense RNA enveloped viruses, members of the family Coronaviridae, that cause infections in a broad range of mammals including humans. Several CoV species lead to mild upper respiratory infections typically associated with common colds. However, three human CoV (HCoV) species: Severe Acute Respiratory Syndrome (SARS)-CoV-1, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV-2, are responsible for severe respiratory diseases at the origin of two recent epidemics (SARS and MERS), and of the current COronaVIrus Disease 19 (COVID-19), respectively. The easily transmissible SARS-CoV-2, emerging at the end of 2019 in China, spread rapidly worldwide, leading the World Health Organization (WHO) to declare COVID-19 a pandemic. While the world waits for mass vaccination, there is an urgent need for effective drugs as short-term weapons to combat the SARS-CoV-2 infection. In this context, the drug repurposing approach is a strategy able to guarantee positive results rapidly. In this regard, it is well known that several nucleoside-mimicking analogs and nucleoside precursors may inhibit the growth of viruses providing effective therapies for several viral diseases, including HCoV infections. Therefore, this review will focus on synthetic nucleosides and nucleoside precursors active against different HCoV species, paying great attention to SARS-CoV-2. This work covers progress made in anti-CoV therapy with nucleoside derivatives and provides insight into their main mechanisms of action.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Drug Repositioning , Nucleosides , SARS Virus/metabolism , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome/drug therapy , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/metabolism , Humans , Nucleosides/chemistry , Nucleosides/therapeutic use , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/metabolism
9.
ChemMedChem ; 16(9): 1403-1419, 2021 05 06.
Article in English | MEDLINE | ID: covidwho-1064335

ABSTRACT

Nucleoside and nucleotide analogues are structurally similar antimetabolites and are promising small-molecule chemotherapeutic agents against various infectious DNA and RNA viruses. To date, these analogues have not been documented in-depth as anti-human immunodeficiency virus (HIV) and anti-hepatitis virus agents, these are at various stages of testing ranging from pre-clinical, to those withdrawn from trials, or those that are approved as drugs. Hence, in this review, the importance of these analogues in tackling HIV and hepatitis virus infections is discussed with a focus on the viral genome and the mechanism of action of these analogues, both in a mutually exclusive manner and their role in HIV/hepatitis coinfection. This review encompasses nucleoside and nucleotide analogues from 1987 onwards, starting with the first nucleoside analogue, zidovudine, and going on to those in current clinical trials and even the drugs that have been withdrawn. This review also sheds light on the prospects of these nucleoside analogues in clinical trials as a treatment option for the COVID-19 pandemic.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Hepatitis, Viral, Human/drug therapy , Nucleosides/therapeutic use , Nucleotides/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Clinical Trials as Topic , Drug Repositioning , HIV/drug effects , HIV/enzymology , HIV Reverse Transcriptase/antagonists & inhibitors , Hepatitis Viruses/drug effects , Hepatitis Viruses/enzymology , Humans , Pandemics , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Reverse Transcriptase Inhibitors/therapeutic use , SARS-CoV-2/drug effects
10.
Eur J Med Chem ; 213: 113201, 2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1039337

ABSTRACT

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Drug Repositioning , Enzyme Inhibitors/therapeutic use , Animals , Antiviral Agents/chemistry , COVID-19/epidemiology , Enzyme Inhibitors/chemistry , Humans , Nucleosides/chemistry , Nucleosides/therapeutic use , Pandemics , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology
11.
Int J Mol Sci ; 21(24)2020 Dec 21.
Article in English | MEDLINE | ID: covidwho-1006952

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) was first identified, the world has vehemently worked to develop treatments and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at an unprecedented speed. Few of the repositioned drugs for COVID-19 have shown that they were efficacious and safe. In contrast, a couple of vaccines against SARS-CoV-2 will be ready for mass rollout early next year. Despite successful vaccine development for COVID-19, the world will face a whole new set of challenges including scale-up manufacturing, cold-chain logistics, long-term safety, and low vaccine acceptance. We highlighted the importance of knowledge sharing and collaboration to find innovative answers to these challenges and to prepare for newly emerging viruses.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Drug Repositioning , Antimalarials/therapeutic use , Chloroquine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Nucleosides/analogs & derivatives , Nucleosides/therapeutic use , Pandemics/prevention & control , Protease Inhibitors/therapeutic use , Public Health , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
12.
Comput Biol Med ; 130: 104185, 2021 03.
Article in English | MEDLINE | ID: covidwho-987393

ABSTRACT

Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking scores and interaction profile analyses exhibited strong binding affinity of eleven FDA approved drugs and five nucleoside analogues NA1 (-13.84), nadide (-13.65), citicholine (-13.54), NA2 (-12.42), and NA3 (-12.27). The lead compound NA1 exhibited significant hydrogen bonding and hydrophobic interaction at the natural substrate binding site. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface (SASA), hydrogen bond formation, principle component analysis, and free energy landscape calculations for NA1 bound protein displayed stable complex formation in 100 ns molecular dynamics simulation, compared to unbound macro domain and natural substrate adenosine-5-diphosphoribose bound macro domain that served as a positive control. The molecular mechanics Poisson-Boltzmann surface area analysis of NA1 demonstrated binding free energy of -175.978 ± 0.401 kJ/mol in comparison to natural substrate which had binding free energy of -133.403 ± 14.103 kJ/mol. In silico analysis by modelling tool ADMET and prediction of biological activity of these compounds further validated them as putative therapeutic molecules against SARS-CoV-2. Taken together, this study offers NA1 as a lead SARS-CoV-2 A1pp domain inhibitor for future testing and development as therapeutics against human coronavirus.


Subject(s)
Antiviral Agents/chemistry , COVID-19/drug therapy , Coronavirus Papain-Like Proteases , Molecular Docking Simulation , Nucleosides/chemistry , SARS-CoV-2/chemistry , Antiviral Agents/therapeutic use , Binding Sites , Coronavirus Papain-Like Proteases/antagonists & inhibitors , Coronavirus Papain-Like Proteases/chemistry , Drug Approval , Humans , Nucleosides/therapeutic use , Protein Binding , United States , United States Food and Drug Administration
13.
Viruses ; 12(11)2020 10 27.
Article in English | MEDLINE | ID: covidwho-895406

ABSTRACT

This is the first report of a successful treatment of a non-effusive feline infectious peritonitis (FIP) uveitis case using an oral adenosine nucleoside analogue drug and feline interferon omega, and alpha-1 acid glycoprotein (AGP) as an indicator of recovery. A 2-year-old male neutered Norwegian Forest Cat presented with uveitis, keratic precipitates, mesenteric lymphadenopathy and weight loss. The cat was hypergammaglobulinaemic and had a non-regenerative anaemia. Feline coronavirus (FCoV) RNA was detected in a mesenteric lymph node fine-needle aspirate by a reverse-transcriptase polymerase chain reaction-non-effusive FIP was diagnosed. Prednisolone acetate eye drops were administered three times daily for 2 weeks. Oral adenosine nucleoside analogue (Mutian) treatment started. Within 50 days of Mutian treatment, the cat had gained over one kilogram in weight, his globulin level reduced from 77 to 51 g/L and his haematocrit increased from 22 to 35%; his uveitis resolved and his sight improved. Serum AGP level reduced from 3100 to 400 µg/mL (within normal limits). Symmetric dimethylarginine (SDMA) was above normal at 28 µg/dL, reducing to 14 µg/dL on the cessation of treatment; whether the SDMA increase was due to FIP lesions in the kidney or Mutian is unknown. Mutian treatment stopped and low-dose oral recombinant feline interferon omega begun-the cat's recovery continued.


Subject(s)
Adenosine/therapeutic use , Feline Infectious Peritonitis/drug therapy , Interferon Type I/therapeutic use , Nucleosides/therapeutic use , Uveitis/drug therapy , Uveitis/veterinary , Adenosine/analogs & derivatives , Animals , Antiviral Agents/therapeutic use , Arginine/analogs & derivatives , Arginine/blood , Cats , Coronavirus, Feline/drug effects , Coronavirus, Feline/isolation & purification , Feline Infectious Peritonitis/diagnosis , Feline Infectious Peritonitis/virology , Glycoproteins/metabolism , Male , Uveitis/diagnosis
14.
Mini Rev Med Chem ; 20(18): 1900-1907, 2020.
Article in English | MEDLINE | ID: covidwho-706996

ABSTRACT

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.


Subject(s)
COVID-19/therapy , Coronavirus 3C Proteases/antagonists & inhibitors , RNA Helicases/antagonists & inhibitors , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Antibodies/therapeutic use , Antiprotozoal Agents/therapeutic use , COVID-19/virology , Coronavirus 3C Proteases/metabolism , Humans , Nucleosides/analogs & derivatives , Nucleosides/metabolism , Nucleosides/therapeutic use , Protease Inhibitors/therapeutic use , RNA Helicases/metabolism , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
15.
Biosci Trends ; 14(1): 69-71, 2020 Mar 16.
Article in English | MEDLINE | ID: covidwho-8442

ABSTRACT

As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Alanine/therapeutic use , COVID-19 , Drug Combinations , Drug Discovery , Humans , Lopinavir/therapeutic use , Neuraminidase/antagonists & inhibitors , Nucleosides/therapeutic use , Ribonucleotides/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2
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