Abstract
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections and deaths worldwide since 2019. The repurposing existing drugs is a practical and promising alternative.
Objectives: To evaluate the binding interactions and inhibitory effect of malaria box compounds on the B-cell epitope regions of SARS-CoV-2 spike protein.
Methods: Molecular docking of 400 malaria box compounds against the predicted B-cell epitopes of the spike was performed. The inhibitory effect of the malaria box compounds on the spike RBD were determined using competitive ELISA. The binding affinity between malaria box compounds and non-RBD epitopes were examined by surface plasmon resonance (SPR) assays.
Results: MMV000563 and MMV019690 were the top-scoring compounds that could bind to the spike RBD with their inhibitory effects at 45.56% and 47%, respectively. However, competitive ELISA revealed that the binding of the spike RBD to human angiotensin-converting enzyme 2 (ACE2) was most strongly inhibited by the compound MMV665881 (P = 0.004). Based on SPR results, the compounds MMV019881, MMV020912, and MMV000753 showed the highest binding affinity to their respective epitope peptides in the non-RBD regions of spike protein.
Conclusion: These results demonstrate the ability of malaria box compounds to bind to and interfere with SARS-CoV-2 spike protein, which may be beneficial for COVID-19 treatment.
DOI
10.56808/2673-060X.5424
Recommended Citation
Sangvansindhu, Chotiyapat
()
"Identification and characterization of malaria box compounds possessing inhibition effect on the SARS-CoV2 spike protein,"
Chulalongkorn Medical Journal: Vol. 68:
Iss.
3, Article 6.
DOI: https://doi.org/10.56808/2673-060X.5424
Available at:
https://digital.car.chula.ac.th/clmjournal/vol68/iss3/6