The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents
an unprecedented challenge to global public health. At the time of this review, COVID-19 has been diagnosed in
over 40 million cases and associated with 1.1 million deaths worldwide. Current management strategies for
COVID-19 are largely supportive, and while there are more than 2000 interventional clinical trials registered
with the U.S. National Library of Medicine (clinicaltrials.gov), results that can clarify benefits and risks of
candidate therapies are only gradually becoming available. We herein describe recent advances in understanding
SARS-CoV-2 pathobiology and potential therapeutic targets that are involved in viral entry into host cells, viral
spread in the body, and the subsequent COVID-19 progression. We highlight two major lines of therapeutic
strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as
antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously
approved for other disease conditions, and 2) novel biological products that are designed to target specific
molecules that are involved in SARS-CoV-2 viral entry, including neutralizing antibodies against the spike
protein of SARS-CoV-2, such as REGN-COV2 (an antibody cocktail), as well as recombinant human soluble ACE2
protein to counteract SARS-CoV-2 binding to the transmembrane ACE2 receptor in target cells. Finally, we
discuss potential drug resistance mechanisms and provide thoughts regarding clinical trial design to address the
diversity in COVID-19 clinical manifestation. Of note, preventive vaccines, cell and gene therapies are not within
the scope of the current review.