An agile discovery method of drugs for infectious diseases and tentative exploration of its application in drug discovery for COVID-19
Chinese Journal of Pharmacology and Toxicology
; 34(6):408-417, 2020.
Article
in Chinese
| CAB Abstracts | ID: covidwho-1863915
ABSTRACT
OBJECTIVE:
To establish an agile discovery method of drugs or natural products for epidemics (aCODE) for the development of anti-infectious disease drugs.METHODS:
Five infectious diseases (HIV infection, human influenza, Paramyxoviridae infections, bacterial infections and whooping cough) involving more than 40 drugs approved by the United States Food and Drug Administration (FDA) were selected. An experimental group and two negative control groups (A and B) for each disease were set up. The experimental group randomly selected (500 times) M FDA-approved indications as seed drugs for the disease, while negative control group A used all FDA-approved infectious drugs for non-current diseases instead of seed drugs, and negative control group B used all non-infectious disease drugs for non-infectious diseases instead of seed drugs. M ranged from 2 to 20, the target gene information of the seed drug was input, and the feature vector of the seed drug set was calculated. Candidate compounds were predicted through similarity search of drug feature vectors. The size of the inter- section between the predicted drug and the positive set of drugs approved by the FDA for the disease, and the significance of the intersection were calculated. After the establishment of the aCODE method, four drugs (lopinavir, ribavirin, ritonavir and chloroquine) were selected as seed drugs for COVlD-19 to predict the composition of natural products. Using natural products with known anti-coronavirus activities as the verification set, the significance of the prediction results was calculated.RESULTS:
In the case of the five infectious diseases, the proportion of positive drugs in the results of prediction in the experimental group increased with the number of seed drugs, while the positive rate of the two negative control groups remained basically unchanged or somewhat trended down. The aCODE method, when applied to COVlD-19 drug screening, could effectively predict drugs with potential anti-SARS-Cov-2 activity (P=0.0046).CONCLUSION:
With the aCODE method, the more the seed drugs, the more accu- rate the characteristics of the disease-related gene modules calculated from this group of seed drugs, and the higher the proportion of positive drugs in the prediction result. This method may contribute to the discovery of drugs for COVID-19.
Prion, Viral, Bacterial and Fungal Pathogens of Humans [VV210]; Pesticides and Drugs; Control [HH405]; Pesticides and Drugs; Chemistry and Formulation [HH420]; Techniques and Methodology [ZZ900]; antimalarials; antiprotozoal agents; chloroquine; coronavirus disease 2019; drug development; drug therapy; human diseases; lopinavir; ribavirin; viral diseases; natural products; human immunodeficiency viruses; HIV infections; influenza; influenza viruses; bacterial diseases; pertussis; antibacterial agents; antiviral agents; screening; genes; prediction; rapid methods; analytical methods; techniques; infections; man; Severe acute respiratory syndrome coronavirus 2; Paramyxoviridae; Bacteria; Bordetella pertussis; Lentivirus; Orthomyxoviridae; Bordetella; Homo; Hominidae; primates; mammals; vertebrates; Chordata; animals; eukaryotes; Severe acute respiratory syndrome-related coronavirus; Betacoronavirus; Coronavirinae; Coronaviridae; Nidovirales; positive-sense ssRNA Viruses; ssRNA Viruses; RNA Viruses; viruses; Mononegavirales; negative-sense ssRNA Viruses; prokaryotes; Alcaligenaceae; Burkholderiales; Betaproteobacteria; Proteobacteria; Orthoretrovirinae; Retroviridae; RNA Reverse Transcribing Viruses; chemotherapy; tribavirin; SARS-CoV-2; viral infections; human immunodeficiency virus infections; flu; bacterial infections; bacterioses; bacterium; whooping cough; antivirals; screening tests; analytical techniques
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Collection:
Databases of international organizations
Database:
CAB Abstracts
Language:
Chinese
Journal:
Chinese Journal of Pharmacology and Toxicology
Year:
2020
Document Type:
Article
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