Introduction: The recent outbreak of coronavirus infection by SARS-CoV-2 that started from the Wuhan Province of China in 2019 has spread to most parts of the world infecting millions of people. Although the case fatality rate of SARS-CoV-2 infection is less than the previous epidemics by other closely related coronaviruses, due to its high infectivity, the total number of SARS-CoV-2 infection-associated disease, called Covid-19, is a matter of global concern. Despite drastic preventive measures, the number of Covid-19 cases are steadily increasing, and the future course of this pandemic is highly unpredictable. The most concerning fact about Covid-19 is the absence of specific and effective preventive or therapeutic agents against the disease. Finding an immediate intervention against Covid-19 is the need of the hour. In this chapter, we have discussed the role of different branches of the cellular proteostasis network, represented by Hsp70-Hsp40 chaperone system, Ubiquitin-Proteasome System (UPS), autophagy, and endoplasmic reticulum-Unfolded Protein Response (ER-UPR) pathway in the pathogenesis of coronavirus infections and in the host antiviral defense mechanisms.Results: Based on scientific literature, we present that pharmacological manipulation of proteostasis network can alter the fate of coronavirus infections and may help to prevent the resulting pathologies like Covid-19. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.