The COVID‐19 pandemic poses a challenge in coming up with quick and effective means to counter its cause, the SARS‐CoV‐2. Here, we show how the key factors governing cysteine reactivity in proteins derived from combined quantum mechanical/continuum calculations led to a novel multi‐targeting strategy against SARS‐CoV‐2, in contrast to developing potent drugs/vaccines against a single viral target such as the spike protein. Specifically, they led to the discovery of reactive cysteines in evolutionary conserved Zn2+‐sites in several SARS‐CoV‐2 proteins that are crucial for viral polypeptide proteolysis as well as viral RNA synthesis, proofreading, and modification. These conserved, reactive cysteines, both free and Zn2+‐bound, can be targeted using the same Zn‐ejector drug (disulfiram/ebselen), which enables the use of broad‐spectrum anti‐virals that would otherwise be removed by the virus's proofreading mechanism. Our strategy of targeting multiple, conserved viral proteins that operate at different stages of the virus life cycle using a Zn‐ejector drug combined with other broad‐spectrum anti‐viral drug(s) could enhance the barrier to drug resistance and antiviral effects, as compared to each drug alone. Since these functionally important nonstructural proteins containing reactive cysteines are highly conserved among coronaviruses, our proposed strategy has the potential to tackle future coronaviruses.