| Full text | |
| Author(s): |
Eberle, Raphael J.
[1, 2]
;
Olivier, Danilo S.
[3]
;
Amaral, Marcos S.
[4]
;
Gering, Ian
[1]
;
Willbold, Dieter
[1, 2, 5]
;
Arni, Raghuvir K.
[6]
;
Coronado, Monika A.
[1, 6]
Total Authors: 7
|
| Affiliation: | [1] Forschungszentrum Julich, Inst Biol Informat Proc IBI Struct Biochem 7, D-52428 Julich - Germany
[2] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Univ Str, D-40225 Dusseldorf - Germany
[3] Fed Univ Tocantins, Campus Cimba, BR-77824838 Araguaina, TO - Brazil
[4] Univ Fed Mato Grosso do Sul, Inst Phys, BR-79070900 Campo Grande, MS - Brazil
[5] Forchungszentrum Julich, JuStruct Julich Ctr Struct Biol, D-52428 Julich - Germany
[6] Univ Estadual Paulista UNESP, IBILCE, Multiuser Ctr Biomol Innovat, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | Viruses-Basel; v. 13, n. 5 MAY 2021. |
| Web of Science Citations: | 1 |
| Abstract | |
Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson \& Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CL(pro)). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CL(pro) but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CL(pro). We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment. (AU) | |
| FAPESP's process: | 16/12904-0 - Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus. |
| Grantee: | Monika Aparecida Coronado |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/05614-3 - Identification of bioactive molecules which inhibit both Chikungunya and Mayaro virus activities. |
| Grantee: | Raphael Josef Eberle |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 18/12659-0 - Mechanisms and Molecular Interactions of Bioactive Molecules with Protein NS3 from Zika Virus - De novo drug design- |
| Grantee: | Monika Aparecida Coronado |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 18/07572-3 - Exploring the non-structural protease nsP2 from Chikungunya and Mayaro viruses: structures and inhibition. |
| Grantee: | Raphael Josef Eberle |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |