The current pandemic of COVID-19 is considered a worldwide threat to public health caused
by a novel type of coronaviridae family called SARS-CoV-2. Owing to the urge of finding a
treatment for this virulent virus, many aspects of drug development are swept aside. This
review aimed to clarify the double-edged sword of drug repurposing in COVID-19 via
summarizing the available treatment options and promising candidates for COVID-19 based
on drug repurposing preclinical studies and in-silico approach. Different drugs target SARS
CoV-2 main structures under clinical investigation; some showed limited efficacy and severe
side effects, while others can be promising solutions. Some drugs suppress the cytokine storm
and modulate immune response during viral infection, including anti-interleukin and
glucocorticoids. Antiparasitic agents are repurposed for SARS-CoV-2 infection management.
Various vaccines and monoclonal antibodies are designed against SARS-CoV-2 and are being
evaluated in different preclinical and clinical stages. However, none of them is approved yet.
Convalescent Plasma Transfusion is a promising strategy against SARS-CoV-2 infection,
where impressive results are reported in clinical trials, requiring more validation. Furthermore,
anticoagulant therapy exhibited better disease outcomes in patients admitted to the ICU.
Finally, in-silico studies suggested several potential compounds or FDA-approved drugs
targeting various viral structure subunits. In conclusion, although many clinical trials were
launched to examine potential therapies based on drug repurposing for COVID-19, there is no
definitive treatment till now. Moreover, computational approaches identified several
compounds and FDA-approved drugs with potential inhibitory effects.