MEK inhibitors reduce cellular expression of ACE2, pERK, pRb while stimulating NK-mediated cytotoxicity and attenuating inflammatory cytokines relevant to SARS-CoV-2 infection

Lanlan Zhou1^,2^,3^,4^,5^,10^,*, Kelsey Huntington1^,2^,4^,5^,6^,10^,*, Shengliang Zhang1^,2^,3^,4^,5^,10, Lindsey Carlsen1^,2^,4^,5^,6^,10, Eui-Young So4^,5^,8, Cassandra Parker1^,2^,4^,5^,7^,10, Ilyas Sahin1^,2^,4^,5^,8^,10, Howard Safran4^,5^,8^,10, Suchitra Kamle4^,5^,9^,10, Chang-Min Lee4^,5^,9^,10, Chun Geun Lee4^,5^,9^,10, Jack A. Elias4^,5^,9^,10, Kerry S. Campbell11, Mandar T. Naik10^,12, Walter J. Atwood4^,5^,10^,13, Emile Youssef14, Jonathan A. Pachter14, Arunasalam Navaraj1^,2^,3^,4^,5^,10, Attila A. Seyhan1^,2^,3^,4^,5^,10, Olin Liang4^,5^,8^,10 and Wafik S. El-Deiry1^,2^,3^,4^,5^,6^,8^,10

1 Brown Experimentalists Against COVID-19 (BEACON) Group, Brown University, Providence, RI 02912, USA

2 Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

3 Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

4 The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI 02912, USA

5 Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

6 Pathobiology Graduate Program, Brown University, Providence, RI 02912, USA

7 Department of Surgery, Lifespan Health System and Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

8 Hematology-Oncology Division, Department of Medicine, Lifespan Health System and Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

9 Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA

10 Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

11 Blood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA

12 Department of Molecular Pharmacology, Physiology and Biotechnology, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

13 Department of Molecular Biology, Cell Biology, and Biochemistry, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

14 Verastem Oncology, Needham, MA 02494, USA

* These authors contributed equally to this work

Correspondence to:

Keywords: ACE2; TMPRSS2; SARS-CoV-2; COVID-19; pseudovirus

Received: October 05, 2020     Accepted: October 17, 2020     Published: November 17, 2020