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Dear Editor,rnCoronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in a severe global pandemic.Following SARS-CoV,SARS-CoV-2 is yet another emergent beta-coronavirus threatening human health.1 However,seventeen years after the SARS pandemic,no targeted vaccines or therapeutics have been approved for SARS,while some of them might have held promise for treating COVID-19.Many neutralizing antibodies against SARS-CoV-2 are currently being developed.However,RNA viruses are known to have high mutation rates.Many SARS-CoV-2 mutations have already been identified such as D614G,2 and these resultant mutation strains might escape the effects of the current SARS-CoV-2 neutralizing antibodies.The appearance of COVID-19 after SARS indicates the likely emergence of other coronavirus pandemics in the future.Thus,therapeutics broadly effective against SARS-CoV-2 and mutants,even other SARS-CoV-2-related coronaviruses(SARSr-CoVs),are highly desirable.Both SARS-CoV-2 and SARS-CoV bind ACE2 for cell entry,suggesting a general use of ACE2 by SARS-CoV-2 mutants and future related coronaviruses.Therefore,proteins engineered based on wild-type ACE2 might exhibit the best broad neutralizing activity and avoid the mutational escape.