Coronavirus Drug Research: Atazanavir Identified As Another Potential Drug Candidate For Coronavirus By AI Platform
Coronavirus Drug Research
Updates : While clinical trials are underway in China on a variety of drugs to treat the new Covid-19 disease including the top three candidates so far which are favipiravir, remdesivri and chloroquine, medical experts and physicianss are still on a look out for newer pharmaceuticals.
Preliminary research data is showing that three present candidates are good for those in early or mid-stages of the Covid-19 diseases, but in patients where the disease has progressed to critical and severe states, the drugs due to their own toxicity are causing complications in treatments.
Earlier HIV anti-virals like lopinavir and ritonavir (sold as Kaletra by AbbVie) seems to be strangely losing it efficacy.
As another resort, some medical, genomic and pharmaceutical researchers are turning to AI or artificial intelligence to quickly find potential anti-virals to test against SARS-CoV-2 coronavirus that causes the Covid-19 disease.
A Korean AI company called Deargen and Dankook University in South Korea in a collaboration with Emory University in the United States, have developed a prediction model for antiviral drugs that may be effective on SARS-CoV-2 coronavirus.
The research is published online at bioRxiv
preprint server .(Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China, through a drug-target interaction deep learning model
Dr Keunsoo Kang, PhD, Assistant Professor at Dankook University and lead researcher told Thailand Medical News
. “It was out of research curiosity that we wanted to look at whether our AI model can suggest any drug that could be used against the SARS-CoV-2 coronavirus.”
The platform entailed a drug repurposing strategy utilizing existing anti-virals that are available on the market and had supporting data already.
The researcher utilized their pre-trained deep learning-based drug-target interaction model, Molecule Transformer-Drug Target Interaction (MT-DTI), to identify commercially available drugs that could act on viral proteins of SAR-CoV-2 coronavirus. The platform is a self-attention-based deep learning model designed for predicting an affinity score between a drug and a protein.
Research results from the study identified atazanavir
, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), as the most promising pharmaceutical candidate.
The researchers indicated that the platform predicted that atazanavir
has an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 coronavirus-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM).
The AI prediction showed that atazanavir
to have a potential binding affinity to multiple components of the coronavirus, binding to RNA-dependent RNA polymerase (Kd 21.83 nM), helicase (Kd 25.92 nM), 3′-to-5′ exonuclease (Kd 82.36 nM), 2′-O-ribose methyltransferase (Kd of 390 nM), and endoRNAse (Kd 50.32 nM), suggesting that all subunits of the SARS-CoV-2 coronavirus replication complex may be inhibited simultaneously by atazanavir.
The researchers speculated that the high antiviral effects of atazanavir may be explained through the AI Platform results showing the highest inhibitory potency on the viral proteinase.
This research was not the first to isolate proteinases as a target for curbing the Covid-19 outbreak that is caused by the SAR-CoV-2 coronavirus. Medical Researchers from Army Medical University in Chongqing, China, had done a another previous research published also in a bioRxiv
preprint titled, “Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening
That research team had utilized high-throughput screening based on 8,000 clinical drug libraries which identified four small molecular drugs that bind the SARS-CoV-2 main protease. The researchers noted that these drugs have been proven to be safe and, therefore, may be promising candidates to use in the current outbreak.
Clinical trials using atazanavir
as an experimental drug has already begun in South Korea but it is too early to assess its efficacy and also its toxicity effects on patients in severe critical conditions.
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