查看更多>>摘要：COVID-19,an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),has spread throughout the world.China has achieved rapid containment of this highly infectious disease following the principles of early detection,early quarantine and early treatment with integrated traditional Chinese and Western medicine.The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence.Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events,improve clinical recovery and help alleviate symptoms such as cough or fever.To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine.The three Chinese patent medicines (Lianhua Qingwen Keli/Jiaonang (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules),Jinhua Qinggan Keli (Honeysuckle Flower Cold-Relieving Granules) and Xuebijing (Stasis-Resolving & Toxin-Removing) Injection were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication.The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.
查看更多>>摘要：Coronaviruses (CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.CoVs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome (SARS),Middle East respiratory syndrome (MERS),and the very recent coronavirus disease 2019 (COVID-19) outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.
查看更多>>摘要：Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises.There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020).SARS-CoV,MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity.To date,there is no specific treatment proven effective against these viral infectious diseases.Vaccination is considered one of the most effective strategies to prevent viral infections.Therefore,the development of effective vaccines against highly pathogenic coronaviruses is essential.In this review,we will briefly describe coronavirus vaccine design targets,summarize recent advances in the development of coronavirus vaccines,and highlight current adjuvants for improving the efficacy of coronavirus vaccines.
查看更多>>摘要：As coronavirus disease 2019 (COVID-19) pandemic poses a substantial global public health threat,traditional Chinese medicine (TCM) was used in 91.50％ of the COVID-19 cases in China,showing encouraging results in improving symptom management and reducing the deterioration,mortality,and recurrence rates.A total of 166 modified herbal formulae consisting of 179 single herbal medicines were collected for treating COVID-19 in China.Glycyrrhizae Radix et Rhizome,Scutellariae Radix,and Armeniacae Semen Amarum are the most frequently utilized in clinics,most of which are antipyretic (47,26.26％),expectorant and cough-suppressing (22,12.29％),and dampness-resolving (21,11.73％) from traditional descriptions.A total of 1212 chemical components containing β-sitosterol,stigmasterol,and quercetin were primarily selected.Additionally,using complex system entropy and unsupervised hierarchical clustering,8 core herbal combinations and 10 new formulae emerged as potentially useful candidates for COVID-19.Finally,following scaffold analysis,self-organizing mapping (SOM) and cluster analysis,12 clusters of molecules yielded 8 pharmacophore families of structures that were further screened as pharmacological targets in human metabolic pathways for inhibiting coronavirus.This article aims to make more easily accessible and share historical herbal knowledge used in contemporary treatments in a modern manner to assist researchers contain the global spread of COVID-19.
查看更多>>摘要：Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole (DIP) in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers (P ＜ 0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5％) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5％) was in clinical remission.
查看更多>>摘要：Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19).To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs (lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID,Days 2 -5:500 mg BID,CQ phosphate),patients with moderate COVID-19 (Day 1: 750 mg and 500 mg,Days 2 -3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations (e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
查看更多>>摘要：The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths.Currently,there is no specific viral protein-targeted therapeutics.Viral nucleocapsid protein is a potential antiviral drug target,serving multiple critical functions during the viral life cycle.However,the structural information of SARS-CoV-2 nucleocapsid protein remains unclear.Herein,we have determined the 2.7(A) crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein.Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain; the surface electrostatic potential characteristics between them are distinct.Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside theβ-sheet core.Complemented by in vitro binding studies,our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain,guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
查看更多>>摘要：A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19).For the purpose,we developed a molecular docking based webserver,namely D3Targets-2019-nCoV,with two functions,one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies,the other is for identifying lead compounds against potential drug targets via docking.This server has its unique features,(1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible;(2) all the potential ligand-binding sites with volume larger than 200 (A)3 on a protein structure were identified for docking;(3) correlation information among some conformations or binding sites was annotated;(4) it is easy to be updated,and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php).Currently,the webserver contains 42 proteins[20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection,replication and release]with 69 different conformations/structures and 557 potential ligand-binding pockets in total.With 6 examples,we demonstrated that the webserver should be useful to medicinal chemists,pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.
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