The present invention relates to an Ace2 variant having enhanced stability through a disulfide bond, an Ace2-Fc fusion protein using same, and a pharmaceutical composition for prevention or treatment of COVID-19. According to the present invention, a disulfide bond is introduced by substituting cysteine for a pair of residues at specific positions of an Ace2 protein, whereby an Ace2 protein variant which is of high binding affinity for SARS-CoV-2 virus and exhibits excellent stability even in an aqueous solution condition can be provided. Accordingly, when the stabilized Ace2 variant of the present invention is applied to a therapeutic agent for the SARS-CoV-2 infection disease COVID-19, the shelf stability, in-vivo stability, and therapeutic effect of the therapeutic agent can be improved. In addition, employing the amino acid sequence derived from the receptor for SARS-CoV-2, the therapeutic agent can effectively work even on various mutant viruses.
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