AXL inhibitors selected by molecular docking: Option for reducing SARS-CoV-2 entry into cells.

The COVID-19 pandemic is ongoing and the benefit from vaccines is still insufficient since COVID-19 continues to be dia g-nosed in vaccinated individuals. It is, therefore, necessary to propose specific pharmacological treatments against COVID-19. A new therapeutic target on the human cellular membrane is AXL (anexelekto), proposed as an independent pathway by which interaction with the S protein of SARS-CoV-2 allows the virus to enter the cell, without the participation of ACE2. AXL serves as another gate through which SARS-CoV-2 can enter cells. Therefore, any stage of COVID-19 could be ameliorated by hindering the interaction between AXL and SARS-CoV-2. This study proposes ten compounds (1-10), selected by mole-cu lar docking and using a library of nearly 500,000 compounds, to develop a new drug that will decrease the interaction of AXL with the S protein of SARS-CoV-2. These compounds have a specific potential site of interaction with AXL, between Glu59, His61, Glu70 and Ser74 amino acids. This site is necessary for the interaction of AXL with the S protein. With this, we propose to develop a new adjuvant treatment against COVID-19.

Identifying compounds that prevent the binding of the SARS-CoV-2 S-protein to ACE2.

We investigated compounds selected by molecular docking to identify a specific treatment for COVID-19 that decreases the interaction between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) of SARS-CoV-2. Five compounds that interact with ACE2 amino acids Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357 were evaluated using specific binding assays for their effects on the interaction between ACE2 with RBD. The compound labeled ED demonstrated favorable ACE2-binding, with an IC50 of 31.95 µM. ED cytotoxicity, evaluated using PC3 cells in an MTT assay, was consistent with the low theoretical toxicity previously reported. We propose that ED mainly interacts with His34, Glu37, and Lys353 in ACE2 and that it has an inhibitory effect on the interaction of ACE2 with the RBD of the S-protein. We recommend further investigation to develop ED into a potential drug or adjuvant in COVID-19 treatment.

Potential inhibitors interacting in Neuropilin-1 to develop an adjuvant drug against COVID-19, by molecular docking.

The COVID-19 pandemic continues without specific treatment. In this study it is proposed compounds that can be developed as adjuvant / complementary drugs against COVID-19. Through a search for molecular docking, for the development of a new drug using pharmacological compounds targeting the b1 region in neuropilin-1 (NRP1), which is important for the interaction with the S1 region of the S-Protein of SARS-CoV-2, to slow down the infection process of this virus. A molecular docking was performed using almost 500,000 compounds targeted to interact in the region between amino acids (Thr316, Asp320, Ser346, Thr349, and Tyr353) in NRP1 to determine compounds able to hinder the interaction with the S1 region in the S-Protein. In this study, ten compounds are proposed as potential inhibitors between S1 region in the S-Protein of SARS-CoV-2 with the b1 region in NRP1, to develop a new adjuvant / complementary drug against COVID-19, and to hinder the interaction between SARS-CoV-2 and human cells, with a high probability to be safe in humans, validated by web servers for prediction of ADME and toxicity (PreADMET).

Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug.

AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of ΔGbinding, the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.