Evaluation of COVID-19 protease and HIV inhibitors interactions

Tran, Linh; Tam, Dao Ngoc Hien; Elhadad, Heba; Hien, Nguyen Minh; Huy, Nguyen Tien

doi:10.2478/acph-2022-0010

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…On the other hand, Tran et al reported favorable affinity (between −5.8 and −8.8 kcal/mol) of NRTIs with SARS-CoV-2 3CLpro [64] , one of the most attractive viral targets for an antiviral drug against this virus [65] . Therefore, we also evaluated the binding affinity of 3TC and FTC with the proteolytic site of 3CLpro, obtaining favorable binding energies, although low, for both compounds ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach

et al. 2023

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<abstract><sec> <title>Background</title> Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico. </sec><sec> <title>Methods</title> The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking. </sec><sec> <title>Results</title> Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from −4.9 kcal/mol to −7.7 kcal/mol) using bioinformatics methods. </sec><sec> <title>Conclusion</title> Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required. </sec></abstract>

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Section: Discussionmentioning

confidence: 99%

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach

et al. 2023

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“…This process involves the prediction of ligand conformation and orientation within a specific binding site, involving algorithms and scoring functions that allow predicting biological activity by evaluating interactions between compounds and potential targets [91]. Both Autodock4 and its graphical interface, AutoDockTools, are available as free and open source software for Microsoft Windows, Mac OS, and Linux systems, Although there is ample evidence of the use of Autodock4 in the search for and development of potential drugs against Cancer, HIV, and COVID-19, among other diseases [92][93][94][95][96][97], its use has also been reported in the training of students in areas related to medicine, bioinformatics, and education [10,[98][99][100].…”

Section: Computational Chemistry Elementsmentioning

confidence: 99%

Constructing a Novel E-Learning Course, Educational Computational Chemistry through Instructional Design Approach in the TPASK Framework

et al. 2023

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The educational scenario after the COVID-19 confinement presents new challenges for teachers. Technological advances require teachers to be prepared for instruction through technology, and with this, the need for e-learning courses arose to strengthen this knowledge. This article aims to describe an innovative e-learning course in Educational Computational Chemistry (ECC) for in-service chemistry teachers through an Instructional Design (ID) that allows the development of the constructs associated with the Technological Pedagogical Science Knowledge (TPASK) framework. From the literature overview, relevant findings were raised concerning ID and its potential technological support. The results indicate that an effective ID must present general elements, such as the organisation and generation of content, progress monitoring, and feedback instances. However, the stages of engagement, flexibility, and positioning are relevant elements. These design elements are linked to emerging technological tools, such as artificial intelligence for generating audiovisual material, interactive content development, and event logs. In addition, positive results are evident from the teachers who participated in the ECC e-learning course, who project the knowledge, computer skills, and learning acquired into their professional work as chemistry teachers. Based on the above, a course design for ECC is proposed with general guidelines that contribute to the continuous training of in-service chemistry teachers.

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“…Nevertheless, the recent reports on the promising use of lopinavir/ritonavir, approved anti-HIV drugs, to inhibit SARS-CoV2 [137,138] might be indicating that the repurpose strategy of HIV proteases for SARS-CoV-2 protease was apparently possible. Thran et al [139] reported that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir demonstrated the promising inhibitory properties against 3CLpro-CoV2 with the binding energy ranging from −8.4 to −9.2 kcal/mol. These compounds are the FDA-approved drugs of HIV.…”

Section: Possibility Of Inhibitors Targeting Hiv Protease For Sars-cov2 Proteasesmentioning

confidence: 99%

Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources

2021

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The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover promising drug targets for the treatment of COVID-19. The SARS-CoV-2 viral proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like cysteine protease (PLpro), have become the promising target to study due to their essential functions in spreading the virus by RNA transcription, translation, protein synthesis, processing and modification, virus replication, and infection of the host. As such, understanding of the structure and function of these two proteases is unavoidable as platforms for the development of inhibitors targeting this protein which further arrest the infection and spread of the virus. While the abundance of reports on the screening of natural compounds such as SARS-CoV-2 proteases inhibitors are available, the microorganisms-based compounds (peptides and non-peptides) remain less studied. Indeed, microorganisms-based compounds are also one of the potent antiviral candidates against COVID-19. Microbes, especially bacteria and fungi, are other resources to produce new drugs as well as nucleosides, nucleotides, and nucleic acids. Thus, we have compiled various reported literature in detail on the structures, functions of the SARS-CoV-2 proteases, and potential inhibitors from microbial sources as assistance to other researchers working with COVID-19. The compounds are also compared to HIV protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors. The information should serve as a platform for further development of COVID-19 drug design strategies.

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Evaluation of COVID-19 protease and HIV inhibitors interactions

Cited by 3 publications

References 25 publications

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach

Constructing a Novel E-Learning Course, Educational Computational Chemistry through Instructional Design Approach in the TPASK Framework

Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources

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