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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312628

ABSTRACT

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here we propose a novel framework, named AIMEE, integrating AI Model and Enzymology Experiments, to identify inhibitors against 3CL protease of SARS-CoV-2, which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value less than 3 μM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and expanding the boundaries of drug discovery.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312627

ABSTRACT

The outbreak of novel coronavirus pneumonia (COVID-19) caused thousands of deaths worldwide, and the number of total infections is still rising. However, the development of effective vaccine for this novel virus would take a few months. Thus it is urgent to identify some potentially effective old drugs that can be used immediately. Fortunately, some compounds that can inhibit coronavirus in vitro have been reported. In this study, the coronavirus-specific dataset was used to fine-tune our pre-trained multi-task deep model. Next we used the re-trained model to select available commercial drugs against targeted proteins of SARS-CoV-2. The results show that abacavir, a powerful nucleoside analog reverse transcriptase inhibitor used to treat HIV, is predicted to have high binding affinity with several proteins of SARS-CoV-2. Almitrine mesylate and roflumilast which are used for respiratory diseases such as chronic obstructive pulmonary disease are also predicted to have inhibitory effect. Overall, ten drugs are listed as potential inhibitors and the important sites for these binding by our model are exhibited. We hope these results would be useful in the fight against SARS-CoV-2.

3.
Vaccines (Basel) ; 9(11)2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1481044

ABSTRACT

Since China's launch of the COVID-19 vaccination, the situation of the public, especially the mobile population, has not been optimistic. We investigated 782 factory workers for whether they would get a COVID-19 vaccine within the next 6 months. The participants were divided into a training set and a testing set for external validation conformed to a ratio of 3:1 with R software. The variables were screened by the Lead Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Then, the prediction model, including important variables, used a multivariate logistic regression analysis and presented as a nomogram. The Receiver Operating Characteristic (ROC) curve, Kolmogorov-Smirnov (K-S) test, Lift test and Population Stability Index (PSI) were performed to test the validity and stability of the model and summarize the validation results. Only 45.54% of the participants had vaccination intentions, while 339 (43.35%) were unsure. Four of the 16 screened variables-self-efficacy, risk perception, perceived support and capability-were included in the prediction model. The results indicated that the model has a high predictive power and is highly stable. The government should be in the leading position, and the whole society should be mobilized and also make full use of peer education during vaccination initiatives.

4.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1348051

ABSTRACT

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 µM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.


Subject(s)
COVID-19/drug therapy , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Small Molecule Libraries/chemistry , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Artificial Intelligence , COVID-19/genetics , COVID-19/virology , Drug Discovery , Humans , Ligands , Protease Inhibitors/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Small Molecule Libraries/therapeutic use
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