ABSTRACT
This paper proposes natural drug candidate compounds for the treatment of coronavirus disease 2019 (COVID-19). We investigated the binding properties between the compounds in the Moringa oleifera plant and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 using molecular docking and ab initio fragment molecular orbital calculations. Among the 12 compounds, niaziminin was found to bind the strongest to Mpro. We furthermore proposed novel compounds based on niaziminin and investigated their binding properties to Mpro. The results reveal that the introduction of a hydroxyl group into niaziminin enhances its binding affinity to Mpro. These niaziminin derivatives can be promising candidate drugs for the treatment of COVID-19.
Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Moringa oleifera/chemistry , Phytochemicals/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Thiocarbamates/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Design , Drug Discovery , Gene Expression , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/classification , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Protease Inhibitors/classification , Protease Inhibitors/isolation & purification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Quantum Theory , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship , Thermodynamics , Thiocarbamates/classification , Thiocarbamates/isolation & purification , Thiocarbamates/pharmacology , COVID-19 Drug TreatmentABSTRACT
[Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses with spike (S) protein projections that allow the virus to enter and infect host cells. The S protein is a key virulence factor determining viral pathogenesis, host tropism, and disease pathogenesis. There are currently diverse corona viruses that are known to cause disease in humans. The occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), as fatal human CoV diseases, has induced significant interest in the medical field. The novel coronavirus disease (COVID-19) is an infectious disease caused by a novel strain of coronavirus (SAR-CoV-2). The SARS-CoV2 outbreak has been evolved in Wuhan, China, in December 2019, and identified as a pandemic in March 2020, resulting in 53.24 M cases and 1.20M deaths worldwide. SARS-CoV-2 main proteinase (MPro), a key protease of CoV-2, mediates viral replication and transcription. SARS-CoV-2 MPro has been emerged as an attractive target for SARS-CoV-2 drug design and development. Diverse scaffolds have been released targeting SARS-CoV-2 MPro. In this review, we culminate the latest published information about SARS-CoV-2 main proteinase (MPro) and reported inhibitors.
Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Phytochemicals/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Amino Acid Sequence , Antiviral Agents/classification , Antiviral Agents/pharmacology , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Discovery , Gene Expression , High-Throughput Screening Assays , Humans , Molecular Docking Simulation , Phytochemicals/classification , Phytochemicals/pharmacology , Protease Inhibitors/classification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship , COVID-19 Drug TreatmentABSTRACT
Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.
Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Herpes Simplex/drug therapy , Influenza, Human/drug therapy , Phytochemicals/therapeutic use , Pneumonia, Viral/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Discovery , HIV/drug effects , HIV/pathogenicity , HIV/physiology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/pathogenicity , Hepacivirus/physiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/pathology , Influenza, Human/virology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Phytochemicals/chemistry , Phytochemicals/classification , Phytochemicals/isolation & purification , Plants, Medicinal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Simplexvirus/drug effects , Simplexvirus/pathogenicity , Simplexvirus/physiology , Virus Internalization/drug effects , Virus Replication/drug effectsABSTRACT
A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography-mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.