https://orcid.org/0000-0003-1000-7508
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ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1–100 μM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.
Acknowledgements
We thank Dr. Tong of the State Key Laboratory of Biotherapy, Sichuan University, for kindly providing the HEK-293T-hACE2 cell line. And we also thank the free online graphic design tool (gdp.renlab.cn) to provide for creating the schematic figures in the paper.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data Availability statement
The data presented in this study are available on request from the corresponding author.
Author contributions
Xu Cao: Conceptualization, Methodology, Investigation, Writing Original Draft. Lan Huang: Investigation and Writing-Review. Min Tang: Methodology, Visualization. Yue Liang and Huijin Hou: Validation. Xinpeng Liu: Investigation, Visualization. Shufang Liang: Conceptualization, Writing-review and editing, funding acquisition.
Abbreviations
DAP: daptomycin; VAN: vancomycin; BLE: bleomycin; PsV: pseudovirus; Ca2+: calcium ions; GFP: green fluorescent protein; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; ACE2: angiotensin-converting enzyme 2.