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1.
Sci Rep ; 11(1): 17748, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1412634

ABSTRACT

Based on WHO reports the new SARS-CoV-2 coronavirus is currently widespread all over the world. So far > 162 million cases have been confirmed, including > 3 million deaths. Because of the pandemic still spreading across the globe the accomplishment of computational methods to find new potential mechanisms of virus inhibitions is necessary. According to the fact that C60 fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets, here the analysis of the potential binding mechanism between SARS-CoV-2 proteins 3CLpro and RdRp with C60 fullerene was done; it has resulted in one and two possible binding mechanisms, respectively. In the case of 3CLpro, C60 fullerene interacts in the catalytic binding pocket. And for RdRp in the first model C60 fullerene blocks RNA synthesis pore and in the second one it prevents binding with Nsp8 co-factor (without this complex formation, RdRp can't perform its initial functions). Then the molecular dynamics simulation confirmed the stability of created complexes. The obtained results might be a basis for other computational studies of 3CLPro and RdRp potential inhibition ways as well as the potential usage of C60 fullerene in the fight against COVID-19 disease.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Fullerenes/pharmacology , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/ultrastructure , Coronavirus Protease Inhibitors/chemistry , Coronavirus Protease Inhibitors/pharmacology , Coronavirus Protease Inhibitors/therapeutic use , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Coronavirus RNA-Dependent RNA Polymerase/ultrastructure , Crystallography, X-Ray , Fullerenes/chemistry , Fullerenes/therapeutic use , Humans , Molecular Dynamics Simulation , Nucleic Acid Synthesis Inhibitors/chemistry , Nucleic Acid Synthesis Inhibitors/pharmacology , Nucleic Acid Synthesis Inhibitors/therapeutic use , Pandemics/prevention & control , RNA, Viral/biosynthesis , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , SARS-CoV-2/ultrastructure
2.
Int J Med Sci ; 17(12): 1803-1810, 2020.
Article in English | MEDLINE | ID: covidwho-647613

ABSTRACT

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Amides/pharmacology , Amides/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Chloroquine/analogs & derivatives , Chloroquine/therapeutic use , Chlorpromazine/therapeutic use , Coronavirus/genetics , Coronavirus Infections/genetics , Cyclophilins/antagonists & inhibitors , Drug Development , Drug Repositioning , Drugs, Chinese Herbal/therapeutic use , Endocytosis/drug effects , Humans , Immune Sera , Interferon Inducers/therapeutic use , Nucleic Acid Synthesis Inhibitors/pharmacology , Nucleic Acid Synthesis Inhibitors/therapeutic use , Pneumonia, Viral/genetics , Pyrazines/pharmacology , Pyrazines/therapeutic use , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2 , Viral Vaccines/therapeutic use , COVID-19 Drug Treatment
3.
Br J Pharmacol ; 177(14): 3147-3161, 2020 07.
Article in English | MEDLINE | ID: covidwho-176068

ABSTRACT

As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , Basigin/metabolism , Benzamidines , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Esters , Gabexate/analogs & derivatives , Gabexate/therapeutic use , Genome, Viral , Guanidines/therapeutic use , Humans , Immunization, Passive , Immunosuppressive Agents/therapeutic use , Medicine, Chinese Traditional , Nucleic Acid Synthesis Inhibitors/therapeutic use , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Protease Inhibitors/therapeutic use , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2 , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Viral Vaccines , Virus Internalization , Virus Replication , COVID-19 Drug Treatment , COVID-19 Serotherapy
4.
Pediatr Infect Dis J ; 39(5): 355-368, 2020 05.
Article in English | MEDLINE | ID: covidwho-101831

ABSTRACT

Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.


Subject(s)
Coronavirus Infections/epidemiology , Animals , Antibodies, Monoclonal/therapeutic use , COVID-19 , Child , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Disease Outbreaks , Humans , Middle East Respiratory Syndrome Coronavirus , Nucleic Acid Synthesis Inhibitors/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Protease Inhibitors/therapeutic use , Severe acute respiratory syndrome-related coronavirus , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/therapy , Vaccines, DNA/therapeutic use , Viral Vaccines/therapeutic use
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