KARIN RUSTLER*, THOMAS BRUCKDORFER
*Corresponding Author
Iris Biotech GmbH, Marktredwitz, Germany

Abstract

With the approval of several COVID-19 vaccines and drugs in recent months, hope is growing that the current pandemic will end soon. However, the rise of new SARS-CoV-2 variants and the possibility of future viral pandemics means that the development of novel therapies cannot stop. Promising therapeutic approaches include repurposing the cancer drug Imatinib and herpes antivirals Penciclovir and Aciclovir, as well as the modification of arginine residues in SARS-CoV-2 proteins using methylglyoxal. Another therapeutic approach that researchers are actively investigating involves inhibitors of the main SARS-CoV-2 protease, M^pro. To facilitate the discovery of effective M^pro inhibitors, we describe two sensitive and convenient assays for rapid screening of drug candidates.

INTRODUCTION

As we take stock of the COVID-19 pandemic in early 2021, more than 146 million people have now been affected by the disease and more than 3.0 million have died. Vaccines and drugs to prevent and treat COVID-19 infection have been and continue to be developed at an extraordinarily rapid pace. Several vaccines have been approved around the world and used to vaccinate hundreds of millions of people in a few short months (1).

Figure 1 illustrates the mechanism of viral entry into the host cell and its proliferation. The infection starts with the docking of the corona viruses spike (S) protein to its receptor called angiotensin-converting enzyme 2 (ACE2) on the host cell’s surface (1). After activation by a cellular surface serine protease (TMPRSS2), the viral S protein becomes fusion competent. Endocytosis (2) and uncoating (3) of the virus allow the release of the viral RNA (4), its replication (5) as well as translation by the host ribosomes (6) to produce viral proteins and proteases. Finally, within the endoplasmic reticulum-golgi intermediate compartment (ERGIC), the viral genome and proteins are assembled to new vi ...