Method
On March 11th, 2020 search engines such as Pubmed, Scopus, Clinicalkey, Cochrane library and Embase were used to search ‘SARS2 and treatment’, ’SARS2 and therapy’, ’COVID 19 and therapy’,’covid19 and treatment’ and ‘COVID 19 and drug’ resulting in a total of 68 articles which 29 articles were excluded due to repetition, irrelevancy, accessibility and language and 24 articles were selected based on a revision of abstracts from the 39 remaining articles. As follow up, another search was conducted on March 22nd 2020 on Pubmed search engine with the “COVID-19 and treatment” keyword, from which 43 articles were selected by titles among 347 results and 40 were chosen further by abstracts.
Finally, on April 5th 2020, the LitCovid engine was searched under the treatment tab from April 1st until April 5th and among 139 of a total of 614 results,17 articles were selected by title which was further narrowed down to 14 due to repetition and irrelevancy based on abstracts. Kowsarpub was also searched for COVID-19 and 14 articles were selected by title in the first step, among which 9 articles remained after further evaluation of abstracts. Pubmed was also searched for “COVID-19 AND favipiravir”,” COVID-19 AND umifenovir”, “COVID-19 AND azithromycin” and “COVID-19 AND plasma therapy” that resulted in 3,4,3 and 7 articles respectively. Later on, “covid-19 AND umifenovir” and “covid-19 AND azithromycin” were narrowed down to 3 and 2 results respectively due to repetition and a lack of compatibility. At last, new drug choices based on computational studies were obtained and articles’ references were evaluated as well.
Pathogenesis
The main cells which are affected by COVID-19 seem to be alveolar type 2 cells which contain Angiotensin Converting Enzyme 2 (ACE 2) (9, 13). Being a member of β-coronaviruses, SARS-CoV-2 has the crown figure on electron microscopic investigation. The spike(S) proteins, the spikes of the crown, bind to ACE2 and facilitates viral attachment through cellular surface into target cells (2). From proteins among members of this family, ACE and ACE2 are of value. Angiotensin II, binds to AT1R on alveolar cells and activates it. ACE converts angiotensin I (produced by enzymatic actions of renin on angiotensinogen) into angiotensin II, a vasoconstrictor agent. ACE2 on the other hand opposes ACE’s function by inactivating angiotensin II and converting it to angiotensin 1-7, a heptapeptide with vasodilator functions. SARS-CoV-2 uses ACE2, as the receptor binding domain (13). Alveolar damage caused by the virus leads to an increase in proinflammatory cytokines (14)causing an interstitial inflammatory infiltration dominated by lymphocytes which contributes to more infiltration ultimately resulting in pneumocytes desquamation and hyaline membrane formation indicating acute respiratory distress syndrome (ARDS) (15).