Talks between Westminster and local leaders over moving Greater Manchester and Lancashire to toughest tier of rules are due to resume later.
Manchester's Labour mayor said the North was being treated with contempt.
But Prof Jeremy Farrar warned making it a north-south or party political issue was "a very dangerous route to go on".
The Wellcome Trust director, who also sits on the Scientific Advisory Group for Emergencies (Sage), told the BBC's Newscast podcast countries that had controlled the virus well so far - including South Korea and New Zealand - had a "national consensus about the way forward".
"I think we've got to come together as a country, this fragmentation, and frankly making this either a north-south or a party political issue, that's a very dangerous route to go on," he said.
"What we don't want now is a fragmentation or confusion - one area or region or city pitched against another. I think that would be very, very damaging to public health and the country's ability to respond."
Sir Jeremy added that negotiations with individual areas caused delays, and he was more in favour of national restrictions.
The prime minister has defended the three-tier system as "the right way forward", which he hoped would "avoid the misery of a national lockdown".
Discussions between central government and leaders in Lancashire are expected to resume at 08:00 BST, while more talks are also expected between leaders in Greater Manchester and No 10 on Friday morning.
From Saturday, people in London, Essex (apart from Southend and Thurrock), York, North East Derbyshire, Chesterfield, Erewash in Derbyshire, Elmbridge in Surrey, and Barrow in Furness, Cumbria will move to the second highest tier - high alert.
This means more than half of England's population will now be living under high or very high-alert restrictions.
So far the Liverpool City Region is the only area in the top tier.
The new three-tier system sees every area of England classed as being on medium, high or very high alert.
Areas on medium alert are subject to the national restrictions currently in force, including the rule of six on indoor and outdoor gatherings and the 22:00 closing time for pubs, bars and restaurants.
In addition to these restrictions, in areas on high alert - which currently includes north-east England, much of the North West and parts of the Midlands, along with West and South Yorkshire - different households are not allowed to mix indoors.
Areas on very high alert face extra curbs, with different households banned from mixing indoors or outdoors in hospitality venues or private gardens.
Pubs and bars will be closed unless they are serving substantial meals and there is also guidance against travelling in and out of the area.
Further restrictions may be agreed for particular regions in the top tier and in the Liverpool City Region gyms, leisure centres, betting shops and casinos have also been forced to close.
For the three-tier system to work, Sir Jeremy said the current level of restrictions would have be toughened up "substantially" and he was more in favour of national restrictions.
"One of the concerns I have is it is sort of dividing up the country when every part of the country is going through an expanding epidemic at the moment in all age groups," he said.
"One of the challenges is the confusion of the messaging. I think on the whole simplicity is easier to understand, it's easier to adhere to, there's a sense that the country is in this together and all parts of the country affected."
He said he would have preferred a "circuit-breaker" - a short, national lockdown - in September, but the "next best" time to act was as soon as possible.
The government is under significant pressure over its approach to local restrictions.
Talks to try to strike an agreement with Greater Manchester will continue on Friday morning - but local leaders in the region are angry and have pledged to fight back against further measures if they are not accompanied by significantly more support, including an improved furlough package for those whose workplaces are forced to close.
The final decision on restrictions rests with ministers - but they desperately want local support for any decision and for now the stand-off continues.
That stand-off is causing dismay among some scientists.
But the government is also facing resistance from its own MPs in Greater Manchester - who fear its plans are too strict.
Meanwhile, conversations on Lancashire moving to the highest tier of restrictions continued late into the night.
Local leaders are considering a package of support offered by ministers but no final decision has bee made yet.
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On Thursday, Greater Manchester's Mayor Andy Burnham said leaders in the region were "unanimously opposed" to a move to the top tier and he called for more financial support for businesses and individuals affected by restrictions.
He said the region was "being set up as the canaries in the coal mine for an experimental regional lockdown strategy".
But Health Secretary Matt Hancock said local leaders should "set aside party politics" and work with the government, with cases rising "exponentially" in the north west of England.
The Labour Mayor of London Sadiq Khan has backed tougher restrictions for the capital but has also called for more financial support.
Meanwhile, the Scottish government is planning to introduce a multi-tier system of alert levels similar to that in England. The country's central belt already faces stricter rules, with pubs and restaurants closed.
In Northern Ireland, schools will close on Monday while, from Friday, pubs, restaurants and cafes will only be allowed to offer takeaway and delivery services for four weeks.
And a ban on travelling to Wales from coronavirus hotspots elsewhere in the UK comes into effect on Friday evening.
On Thursday, a further 18,980 cases and 138 deaths within 28 days of a positive test were reported across the UK.