Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.
نویسندگان
چکیده
The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M(pro)), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC(50) of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M(pro), Hel, and viral entry, respectively, exhibited potent antiviral activity (EC(50) < 10 microM) and comparable inhibitory activities in target-specific in vitro assays.
منابع مشابه
Study of the Clinical and Radiologic findings of Middle East Respiratory Syndrome and Coronavirus Disease-2019
Aim and Background: Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) is a single-strand RNA, β‐coronavirus with mostly respiratory symptoms responsible for Corona Virus Disease (COVID-19), which causes a pandemic worldwide. This novel coronavirus is associated with severe pneumonia and Acute Respiratory Distress Syndrome (ARDS). Middle East Respiratory Syndrome (MERS-CoV) is another ...
متن کاملCoronavirus 2 Acute respiratory syndrome: Emergence, Evolution and thrapeutic prevention strategies
The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, and spread all over the world. In a phylogenetic network analysis of human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, three central variants were distinguished by amino acid changes, which named A, B, and C; with A being the ancestral type a...
متن کاملGastrointestinal Manifestations in Patients Infected with SARS-CoV-2
Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, has recently become the number one problem affecting global health. Coronavirus disease 2019 is principally recognized by its respiratory manifestations; however, recent studies have shown an increasing number of patients with gastrointestinal complaints like diarrhea, nausea, vomiting, and abdominal discomfort...
متن کاملPromising role of Bruton’s Tyrosine Kinase Inhibitors in Treatment of COVID-19
Severe acute respiratory syndrome coronavirus-2 has led to a widespread pandemic whose spread is astonishing, its treatment is uncertain, mortality is significant, and associated socioeconomic complications are uncontrollable. Although little is known about the pathogenesis of the disease, severe cases of COVID-19 are usually associated with cytokine release syndrome and high serum levels of in...
متن کاملIdiosyncrasies of COVID-19; A Review
The Coronavirus disease 2019, identified by Chinese researchers to be the caused by a novel enveloped betacoronavirus, Severe Acute Respiratory Syndrome Coronavirus- 2 which was first isolated in Wuhan, China has been declared a global pandemic by the world health organization. The virus has several structural proteins that contributed to its pathogenesis such as spikes, membrane, envelop and n...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chemistry & biology
دوره 11 9 شماره
صفحات -
تاریخ انتشار 2004