en Pulmonary Disease Pulmonary Disease Original Research Original Research <strong>&nbsp;&nbsp;</strong><strong>&nbsp; Background: </strong>Coronavirus disease 2019 (COVID-19) is caused by a new severe acute respiratory syndrome Coronavirus. COVID-19 patients are at risk for acute respiratory distress syndrome and death from respiratory failure.<br> &nbsp;&nbsp; <strong>Methods:</strong> In this study the complete genome of the SARS-CoV-2 reference sequence, geologically isolated types, and Coronavirus related to human diseases were compared by the Molecular Phylogenetic Maximum Likelihood method. The secondary and tertiary structures of the main protease of SARS-CoV were defined as the most similar viruses to SARS-CoV-2, aligned with chimera software. Therefore, considering ineffective antiviral medications used for SARS-CoV and the importance of preventing acute respiratory distress syndrome as the main cause of mortality, 2 strategies were adopted to acquire the most effective drug combination.<br> &nbsp;&nbsp; <strong>Results: </strong>The results of phylogenic analysis showed that SARS-CoV is the most similar virus to SARS-CoV-2. The secondary structure and superimposing of tertiary structure did not show a significant difference between SARS and SARS-CoV-2 3C-like main protease and the root means square deviation between C&alpha; atoms did not support the difference between the 2 protein structures. Thus, these 2 mechanisms were fostered in accordance with the correlation between acute respiratory distress syndrome-related Coronavirus, angiotensin-converting enzyme 2 on one side and the possible treatments for reducing the respiratory side effects on the other. The analysis of renin-angiotensin system as well as the tested drugs applied to acute respiratory distress syndrome cases, indicated that angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and C21 as nonpeptide agonist might possess a promising modality of treatment for acute respiratory distress syndrome. Furthermore, implementing recombinant human ACE2 as a competitive receptor might be an effective way to trap and chelate the SARS-CoV-2 particles.<br> &nbsp;&nbsp; <strong>Conclusion:</strong> The data suggest that combination therapy of angiotensin II receptor blockers and C21 could be a potential pharmacologic regimen to control and reduce acute respiratory distress syndrome. Moreover, rhACE2 can be recommended as an effective protective antiviral therapy in the treatment of COVID-19 and its complications. Acute respiratory distress syndrome, SARS-Associated Coronavirus, Renin-Angiotensin system, SARS-CoV-2 818 827 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-5854-1&slc_lang=en&sid=1 Marzieh Soheili soheili_md@yahoo.com 200319475328460064358 200319475328460064358 No Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, & Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran Kaveh Haji-allahverdipoor kaveh.allahverdipoor@gmail.com 200319475328460064359 200319475328460064359 No Department of Biotechnology and Plant Breeding, Faculty of Agriculture, Tarbiat Modares University, & Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran, Iran Mohamad Bagher Khadem-erfan khademerfan@gmail.com 200319475328460064360 200319475328460064360 No Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran Babak Baban bbaban@augusta.edu 200319475328460064361 200319475328460064361 No Department of Oral Biology and Diagnostic Sciences, DCG, Augusta University, Augusta GA, USA Bahram Nikkhoo B.Nikkhoo@gmail.com 200319475328460064362 200319475328460064362 No Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, & Department of Pathology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran Anwar Eliasi a_eliasi@yahoo.com 200319475328460064363 200319475328460064363 No Department of Surgery, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran Sherko Nasseri sherko.nasseri@muk.ac.ir 200319475328460064364 200319475328460064364 Yes Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran