Computational search for potential COVID-19 drugs from FDA-approved drugs and small molecules of natural origin identifies several anti-virals and plant products

Abstract

The world is currently facing the COVID-19 pandemic, for which mild symptoms include fever and dry cough. In severe cases, it could lead to pneumonia and ultimately death in some instances. Moreover, the causative pathogen is highly contagious and there are no drugs or vaccines for it yet. The pathogen, SARS-CoV-2, is one of the human coronaviruses which was identified to infect humans first in December 2019. SARS-CoV-2 shares evolutionary relationship to other highly pathogenic viruses such as Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS). We have exploited this similarity to model a target non-structural protein, NSP1, since it is implicated in the regulation of host gene expression by the virus and hijacking of host machinery. We next interrogated the capacity to repurpose around 2300 FDA-approved drugs and more than 3,00,000 small molecules of natural origin towards drug identification through virtual screening and molecular dynamics. Interestingly, we observed simple molecules like lactose, previously known anti-virals and few secondary metabolites of plants as promising hits. These herbal plants are already practiced in Ayurveda over centuries to treat respiratory problems and inflammation. Disclaimer: we would not like to recommend uptake of these small molecules for suspect COVID patients until it is approved by competent national or international authorities.

Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19

“…Two of these drugs, Bosutinib and Ponatinib, are inhibitors of SRC and were patented as also being capable of blocking cell surface HSPA5 expression ( http://www.freepatentsonline.com/y2019/0076431.html ). Natural products may also interfere with SARS-CoV-2 attachment to stressed cells, which is worth of further investigation 23 , 113 .…”

Computationally approached inhibition potential of Tinospora cordifolia towards COVID-19 targets

“…Recently, many natural products [28,56] and refurbished drugs are reported in the literature as possible drug candidates for COVID-19. The broad spectrum therapeutic significance of Tinospora cordifolia has paved way for their investigation as potent inhibitors for SARS-CoV-2.…”

“…Moreover, to devise therapeutic strategies, it is important to know how the virus invades the humans during infection and this knowledge can be applied to develop new drugs and to repurpose the existing ones [24]. There are also reports on various constituents from plants [25] of medicinal values as potential inhibitors and anti-viral drugs [26][27][28].…”

“…With the available scientific approaches and computational facilities to model proteins and investigate proteinligand interactions it becomes more supportive to predict the binding of small molecular drugs to protein targets [28,37,38]. Employing density functional theory [39] the geometry of all the molecules proposed as COVID-19 drug candidates, were optimized to understand structural features and hence their contribution to the inhibition or druggable potential.…”

Targeting multiple conformations of SARS-CoV2 Papain-Like Protease for drug repositioning: An in-silico study

“…Structure-based virtual screening (SBVS) remains an essential technique in modern drug discovery[ [18] , [19] , [20] , [21] ]. Molecular docking is widely employed in SBVS campaigns and computational drug repositioning for COVID-19[ [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ], utilizing the structural information of the protein targets to gauge molecular databases and predict the favored binding of compounds. However, the docking tool should be evaluated utilizing benchmarking molecular sets[ 31 , 32 ].…”