Journal of Clinical Infectious Diseases & Practice
Open Access

Coronaviruses; Protein intrinsic disorder; Viral transmission

Introduction

Coronaviruses, a family of enveloped RNA viruses, have gained global attention due to the outbreaks caused by severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and the novel coronavirus SARS-CoV-2 responsible for COVID-19. The ability of these viruses to rapidly transmit among humans necessitates a deeper understanding of their molecular mechanisms, particularly their protein structures and behaviors. In this article, we delve into the concept of protein intrinsic disorder and its potential implications for the viral transmission of coronaviruses [1].

The HIV and EIAV viruses, that are related but have distinctly different modes of transmission, were used to illustrate this point since. HIV is largely transmitted sexually, whereas EIAV is transmitted by a blood-sucking horsefly. It has been observed that the abundance of predicted intrinsic disorder (PID) in the HIV and EIAV matrix proteins was very different, with the HIV proteins being highly disordered, especially HIV-1. An explanation for this has to do with the need for a more rigid encasement in viruses that are not sexually transmitted, so as to protect the virion from harsher environmental factors [2].

Protein intrinsic disorder in viral proteins

Proteins in coronaviruses play a crucial role in viral replication, host interactions, and immune evasion. Intriguingly, many viral proteins possess regions of intrinsic disorder, characterized by the lack of stable secondary or tertiary structures. These disordered regions are flexible and versatile, enabling proteins to interact with various cellular partners, which may facilitate viral transmission and replication.

Predicting intrinsic disorder in coronaviruses proteins

Advancements in bioinformatics have provided powerful tools for predicting intrinsic disorder in protein sequences. By employing algorithms such as PONDR, IUPred, and DISOPRED, researchers can identify and characterize disordered regions in coronaviral proteins. Analyzing the distribution and properties of intrinsic disorder within viral proteins can offer insights into their functional roles during the viral life cycle [3].

Implications of protein intrinsic disorder on viral transmission

The presence of intrinsic disorder in coronaviruses' structural and non-structural proteins has been associated with several crucial processes, including viral entry, replication, and evasion of host immune responses. Understanding the role of intrinsic disorder in viral transmission can shed light on the molecular determinants of virulence and pathogenesis.

Targeting intrinsic disorder for therapeutic interventions The flexible nature of intrinsically disordered regions makes them challenging targets for traditional drug design [4]. However, novel approaches, such as small molecule inhibitors or peptides that mimic key interactions, could be developed to disrupt critical protein-protein interactions involving disordered regions, thereby inhibiting viral transmission.

Discussion

In fact, there is a correlation between the PID levels and the localization of surface proteins, with proteins located closer to the virion surface being generally more rigid than other surface proteins [5, 6]. Generally, the stepwise decrease in the PIDs is seen for all viral nucleocapsid, capsid, and matrix proteins analyzed so far.

Disorder peculiarities can be potentially mapped to the transmission behavior and the nature of the viruses. It can be seen that in comparison with other viruses, the coronaviruses possess a tendency to be more ordered at the level of the matrix proteins [7], but their nucleocapsid proteins are generally more disordered than nucleocapsid proteins RNA viruses in general. The fact that both influenza viruses and coronaviruses have high predicted disorder in their nucleocapsid proteins suggests that higher nucleocapsid disorder may be necessary for viruses with ability to spread via respiratory means. Further support for this hypothesis will be presented below as we inspect and categorize the various coronaviruses. Past analysis showed that many viruses that spread by respiratory modes are characterized by disordered shell proteins [8].

Obviously, the environmental conditions associated with the respiratory transmission are less harsh than those seeing in the fecaloral transmission mode. However, the viruses that are spread via the respiratory mode might experience greater environmental pressure during transmission and they have to be able to adjust to a greater range of environmental changes to survive and to be successfully transmitted [9]. This ability of the respiratory transmitted viruses to adjust and survive in a wide range of conditions can be due to the higher levels of intrinsic disorder in their shell proteins. In other words, shell proteins of these viruses are assembled into a flexible shield, the pliability of which helps viruses to rapidly adjust to the environmental changes. Table 3 supports this hypothesis by showing that for several viruses analyzed, there is a noticeable correlation between the level of disorder in the shell proteins and the transmission mode [10].

Conclusion

Predicting protein intrinsic disorder in coronaviruses provides valuable insights into their structural dynamics and functional roles during viral transmission. Understanding the molecular basis of viral transmission can guide the development of targeted therapies and preventive strategies to combat future coronavirus outbreaks. By harnessing the power of bioinformatics and structural biology, we aim to make significant strides in mitigating the impact of coronaviruses on global health.

1. Kobo O, Nikola S, Geffen Y, Paul M (2017) The pyogenic potential of the different Streptococcus anginosus group bacterial species: retrospective cohort study. Epidemiol Infect 145:3065-3069.

Indexed at, Google Scholar, Crossref

2. Noguchi S, Yatera K, Kawanami T, Yamasaki K, Naito K, et al. (2015) The clinical features of respiratory infections caused by the Streptococcus anginosus group. BMC Pulm Med 26:115:133.

Indexed at, Google Scholar, Crossref

3. Yamasaki K, Kawanami T, Yatera K, Fukuda K, Noguchi S, et al. (2013) Significance of anaerobes and oral bacteria in community-acquired pneumonia. PLoS One 8:e63103.

Indexed at, Google Scholar, Crossref

4. Junckerstorff RK, Robinson JO, Murray RJ (2014)  Invasive Streptococcus anginosus group infection-does the species predict the outcome? Int J Infect Dis 18:38-40.

Indexed at, Google Scholar, Crossref

5. Okada F, Ono A, Ando Y, Nakayama T, Ishii H, et al. (2013) High-resolution CT findings in Streptococcus milleri pulmonary infection. Clin Radiol 68:e331-337.

Indexed at, Google Scholar, Crossref

6. Gogineni VK, Modrykamien A (2011) Lung abscesses in 2 patients with Lancefield group F streptococci (Streptococcus milleri group). Respir Care 56:1966-1969.

Indexed at, Google Scholar, Crossref

7. Kobashi Y, Mouri K, Yagi S, Obase Y, Oka M (2008)  Clinical analysis of cases of empyema due to Streptococcus milleri group. Jpn J Infect Dis 61:484-486.

Indexed at, Google Scholar                    

8. Shinzato T, Saito A (1994) A mechanism of pathogenicity of "Streptococcus milleri group" in pulmonary infection: synergy with an anaerobe. J Med Microbiol 40:118-123.

Indexed at, Google Scholar, Crossref

9. Zhang Z, Xiao B, Liang Z (2020) Successful treatment of pyopneumothorax secondary to Streptococcus constellatus infection with linezolid: a case report and review of the literature. J Med Case Rep 14:180.

Indexed at, Google Scholar, Crossref

10. Che Rahim MJ, Mohammad N, Wan Ghazali WS (2016) Pyopneumothorax secondary to Streptococcus milleri infection. BMJ Case Rep bcr 2016217537.

Indexed at, Google Scholar, Crossref