Recombinant ACE2-Fc fusion molecules and methods of making and using thereof

A method of preventing, reducing a risk of, or treating a virus infection, or preventing or treating a symptom caused by the virus in a subject, said method comprising administering to said subject an effective amount of a fusion protein, wherein the fusion protein comprises a variant angiotensin converting enzyme 2 (ACE2) domain covalently fused to a Fc domain. The variant ACE2 domain comprises a N-terminal deletion, a C-terminal deletion, or both, relative to a full-length wildtype ACE2 having a SEQ ID NO. 1, and the variant ACE2 domain has ACE2 activity. The virus may be SARS-CoV, SARS-CoV-2, or MERS-CoV. The symptom comprises Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome (ARDS), Pulmonary Arterial Hypertension (PAH), or Coronavirus Disease 2019 (COVID-19).