IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) has led to the rapid initiation of urgently needed clinical trials of repurposed drug combinations and monotherapies. These regimens were primarily relying on mechanism-of-action based selection of drugs, many of which have yielded positive in vitro but largely negative clinical outcomes. To overcome this challenge, we report the use of IDentif.AI, a platform that rapidly optimizes infectious disease (ID) combination therapy design using artificial intelligence (AI). In this study, IDentif.AI was implemented on a 12-drug candidate therapy search set representing over 530,000 possible drug combinations. IDentif.AI demonstrated that the optimal combination therapy against SARS-CoV-2 was comprised of remdesivir, ritonavir, and lopinavir, which mediated a 6.5-fold improvement in efficacy over remdesivir alone. Additionally, All rights reserved. No reuse allowed without permission.was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Artificial Intelligence Effecting a Paradigm Shift in Drug Development

“…On the other hand, combinatorial hydroxychloroquine and azithromycin were shown to be relatively ineffective. 73 Completed within 2 wk, these studies also demonstrate the application and translational capabilities of AI to identify optimal therapeutics from the existing pool of drugs to address future outbreaks.…”

Yapay Zeka'nın Mikrobiyolojide Kullanımı

“…Hedef proteininin kimyasal sekanslarına ve aminoasit sekanslarına dayalı bağlanma afinitelerini doğru bir şekilde tahmin eden yapay zeka, insan immün yetmezlik virüsünü (HIV) tedavi etmek ve önlemek için kullanılan Atazanavir'in, inhibe edici bir etki gösteren en iyi kimyasal bileşik olduğunu göstermiştir. Atazanavir'in ardından etkili bileşikler arasında Şekil 3'te görüldüğü gibi remdesivir, efavirenz, ritonavir ve dolutegravir gelmektedir (64).…”

“…Koronavirüs hastalığının tanımlanmasında BT görüntülerini kullanan derin öğrenme algoritmaları(49).Şekil 2. Yapay zeka ile önerilen etkili antiviral bileşikler(64).…”

The New Technologies in the Pandemic Era

“…Blasiak and colleagues [70] described the use of IDentif.AI, a platform that quickly optimizes infectious disease (ID) combination therapy design applying artificial intelligence (AI). The platform IDentif.AI was realized on a 12drug candidate therapy search set representing over 530,000 possible drug combinations.…”