Curcumin ‘cure’ for Omicron variant of COVID-19

•Study shows lower SARS-CoV-2 mortality among physically active individuals in Sub-Saharan Africa

A recent study published in the journal Computers in Biology and Medicine demonstrated that the phytochemical curcumin is a potent therapeutic prospect against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

The ongoing COVID-19 pandemic has caused over 508 million SARS-CoV-2 cases and six million deaths to date globally. As of now, the SARS-CoV-2 Omicron (B.1.1.529) variant is the dominant strain worldwide. Omicron was designated a variant of concern (VOC) since it can evade vaccine- and infection-induced immunity due to several mutations in its spike (S) protein, including 15 amino acid substitutions across the receptor-binding domain (RBD).

Recent studies indicate that many of the most widely used COVID-19 vaccinations offer little or no immunity against Omicron infection. To date, no specific therapeutic regimen for this VOC has been recommended. As a result, Omicron might jeopardize worldwide attempts to contain the COVID-19 pandemic by posing a public health risk.

The present paper aimed to profile seven phytochemicals (capsaicin, gingerol, allicin, curcumin, piperine, zingeberene, and cinnamaldehyde) and discover possible therapeutic options against the Omicron variant. The researchers built a three-dimensional layout of Omicron S RBD by integrating 15 amino acid alterations to the Native S structure. The team contrasted the structural changes of the Omicron S with the Native S. The authors docked the seven phytochemicals with the Omicron S-human angiotensin-converting enzyme 2 (hACE2) complex and the Omicron S protein.

In addition, a molecular dynamic (MD) simulation was run between the curcumin and Omicron S protein to assess the structural stability of the complex in a physiological setting. Further, the team compared the results to the control medication chloroquine and GR 127935 hydrochloride.

The Native S protein’s main sequence (starting position 333) was acquired from the global initiative on sharing all influenza data (GISAID). Fifteen mutations were introduced into Native S using the PyMol 2.5 software, resulting in Omicron S. The UCSF Chimera software was used to examine and visualize the impact of mutations on the Omicron S protein.

The hACE2 and Omicron S proteins binding were performed using the ClusPro protein-protein docking webserver. The seven phytochemicals with the Omicron S and Omicron S-hACE2 complex were docked using the Dockthor docking server. The free energies of curcumin-Omicron S and chloroquine-Omicron S complexes were calculated using the molecular mechanics-Poisson–Boltzmann solvent-accessible surface area (MM-PBSA) approach. Finally, the PyMol 2.5 software was used to assess the impact of curcumin interaction with the target protein Omicron S.

The study results showed that the amino acid substitutions in the SARS-CoV-2 Omicron variant could favour improved binding capacity to hACE2, potentially resulting in increased SARS-CoV-2 viral transmissibility. Prodigy assessment showed that the binding energy between Omicron S protein and hACE2 was -13.7 Kcal mol-1. While the binding energies of the projected S and Omicron S proteins were comparable, Native S had a modest binding potential with hACE2. Compared to the corresponding control medicines, the curcumin attached considerably with both the Omicron S/hACE2 complex and Omicron S.

ALSO, a recent review in Progress in Cardiovascular Diseases enlisted the benefits of physical activity (PA) and being outdoors in reducing the incidence, prevalence, and severity of coronavirus disease 2019 (COVID-19) among low-income and underserved populations such as sub-Saharan Africans.

The study titled, “Why are COVID-19 effects less severe in Sub-Saharan Africa? Moving more and sitting less may be a primary reason”, was published in the journal Progress in Cardiovascular Diseases.

COVID-19 has taken a devastating toll on human lives with significant morbidity and mortality across the globe. It is well established that the risk of COVID-19 severity outcomes such as increased hospitalisations and deaths are higher among the elderly, immuno-compromised individuals with chronic comorbidities such as diabetes and hypertension.

The COVID-19 severity risk is also higher among obese and physically inactive individuals with unhealthy lifestyle habits such as lack of exercise, unhealthy diets, and smoking.

Another aspect to be taken into consideration is the health inequalities among the developed and developing nations. COVID-19 burden has been higher among low-income nations such as the sub-Saharan regions of Africa. Poverty, crowding, fewer medical resources, inadequate healthcare facilities, and vaccination uptake could be reasons for the catastrophic impact of COVID-19 among the underserved populations. In contrast, Africa has witnessed a less profound impact of COVID-19, based on articles in the New York Times and The Economist.

An understanding of the reasons for the lower COVID-19 severity in Africa could bring to light mechanisms to improve the COVID-19 impact in other low-income nations and decrease the global burden of COVID-19.

PA leads to lower levels of systemic inflammation, improved immune functioning, reduced rate of infections, less inflammation, decreased severity of infection outcomes, and improved vaccine efficacy, particularly in immuno-compromised individuals. Such benefits of PA should result in improved cardiopulmonary fitness and enhanced immune resiliency during the pandemic.

A recently published multinational systematic review conducted by the United States (US) Centers for Disease Control and Prevention (CDC) that included 25 COVID-19 outcome-specific studies concluded that physically fit or active individuals prior had a reduced likelihood of being hospitalized or dying due to COVID-19. However, the evidence of a lower likelihood of intensive care unit (ICU) admissions or ventilation requirements in physically active individuals was lower. The CDC review underscored the importance of PA in improved COVID-19 severity outcomes and established lack of exercise as an important risk factor for severe COVID-19.

Another large-scale study that assessed the impact of PA on COVID-19 outcomes using several device-based PA measures on 65,361 South African individuals confirmed the findings of the CDC review, underpinning the protective effects of PA against COVID-19.

Several studies have reported that Africans are significantly more physically fit or active compared to those in Europe or the US. However, obesity is scaling up in Africa, and measures must be taken to reduce the body mass of Africans to prevent severe COVID-19 outcomes in these populations in the future.

Generally, African individuals spend more hours outdoors daily, particularly those residing in rural areas or outskirts of cities. Several commonly performed leisure activities such as running, walking, digging; cycling, playing soccer, dancing, and swimming are performed in the outdoor environment.

Another aspect to consider is that most Africans did not substantially decrease their PA during the COVID-19 pandemic since PA is a part of their activities for earning a livelihood. For example, most Africans have to travel daily as part of their daily jobs, for which they rely on public transportation since a majority of them do not have the economic capacity to own private vehicles. These economically deprived individuals, most belonging to underprivileged households, rarely rely on digitized and motorized equipment and gadgets. Their means of economic sustenance are based on small-scale, informal, and labor-intensive businesses such as farming, which requires considerable movement of light or moderate intensities. Thus, moving more and sitting less is a feature of their standard of living.

This review highlights that sub-Saharan Africa is in a much better state compared to other low-income nations in terms of protection against the ongoing COVID-19 pandemic. The preparedness of sub-Saharan Africans residing in rural areas and practicing labor-intense, agricultural, and related small businesses toward the COVID-19 pandemic is much better compared to individuals residing in urban areas and higher-income nations such as Europe and the US. The authors believe that the improved pandemic fitness could be due to an overall younger age and regular PA, as part of the daily activities performed for their economic survival.

The review findings underpin the importance of PA in decreasing the incidence, prevalence of severity of the COVID-19 pandemic. This indicates that despite limited access to healthcare facilities and low availability of medical resources, low-income nations could improve their immune protection against COVID-19 by improving the physical fitness of their residents. Measures and strategies must be undertaken by all individuals to decrease obesity and inculcate good lifestyle habits into their daily routine to prevent the devastating effects of COVID-19 on their health.